Lens-free tomographic imaging devices and methods

Abstract

A system for three dimensional imaging of an object contained within a sample includes an image sensor, a sample holder configured to hold the sample, the sample holder disposed adjacent to the image sensor, and an illumination source comprising partially coherent light. The illumination source is configured to illuminate the sample through at least one of an aperture, fiber-optic cable, or optical waveguide interposed between the illumination source and the sample holder, wherein the illumination source is configured to illuminate the sample through a plurality of different angles.

1 - 35 . (canceled) 
     
     
         36 . A lens-free system for three dimensional imaging of an object contained within a sample comprising:
 a stationary image sensor;   a sample holder configured to hold the sample, the sample holder disposed adjacent to the image sensor at a distance of z 2 ;   an illumination source comprising partially coherent light or coherent light and located a distance z 1  from the sample holder and wherein the sample is disposed adjacent to the image sensor at a distance z 2 , wherein z 2 <<z 1 , the illumination source configured to illuminate the sample through at least one of an aperture, fiber-optic cable, or optical waveguide interposed between the illumination source and the sample holder, wherein the illumination source is configured to illuminate the sample through a plurality of different angles;   means for jogging at least one of the aperture, fiber-optic cable, or optical waveguide in a plane substantially parallel with an imaging plane in x and y directions at a plurality of different jog locations and obtaining lens-free hologram images of the object in the sample at the different jog locations at each of the plurality of different angles; and   one or more processors configured to reconstruct a three dimensional tomographic image of objects within the sample based on images obtained from by the stationary image sensor at the plurality of different angles and jog locations.   
     
     
         37 . The system of  claim 36 , wherein at least one of the illumination source and the sample holder are moveable relative to each other. 
     
     
         38 . The system of  claim 36 , wherein the sample holder comprises a microfluidic flow cell. 
     
     
         39 . The system of  claim 38 , wherein the sample holder is angled with respect to the image sensor. 
     
     
         40 . The system of  claim 36 , wherein the plurality of different angles span a range between about −89° to +89°. 
     
     
         41 . The system of  claim 36 , wherein the means for jogging comprises at least one of a stepper motor, moveable stage, piezoelectric element, electromagnetic actuator, and solenoid and the means for jogging effectuates small displacement jogs that are less than about 70 μm. 
     
     
         42 . The system of  claim 36 , wherein the plurality of angles comprises different angles along a surface of a three dimensional shape. 
     
     
         43 . The system of  claim 36 , wherein the illumination source comprises a plurality of individual light sources operatively coupled to a microcontroller configured to selectively activate individual light sources 
     
     
         44 . A method of obtaining a three dimensional image of an object contained within a sample without a lens comprising:
 illuminating a sample holder configured to hold the sample with an illumination source emitting partially coherent light or coherent light at a first angle, the light passing through at least one of an aperture or a fiber-optic cable prior to illuminating the sample and wherein the illumination source is located a distance z 1  from the sample;   illuminating the sample holder with the illumination source at different angles, the light passing through the aperture or the fiber-optic cable prior to illuminating the sample;   obtaining, at each angle, a plurality of sub-pixel, lens-free hologram image frames of the object from a stationary image sensor disposed on an opposing side of the sample holder, wherein the sub-pixel, lens-free hologram image frames are each obtained by jogging at least one of the aperture or fiber-optic cable in a plane substantially parallel to the image sensor in x and y directions and wherein the sample is disposed adjacent to the image sensor at a distance z 2 , wherein z 2 <<z 1 ;   digitally converting the sub-pixel, lens-free hologram image frames at each angle into a single higher resolution hologram for each angle;   digitally reconstructing projection images for each angle from the higher resolution holograms; and   digitally back projecting three dimensional tomographic images of the object within the sample.   
     
     
         45 . The method of  claim 44 , wherein the plurality of angles comprise a plurality of angles in a single plane or multiple planes. 
     
     
         46 . The method of  claim 44 , wherein the plurality of angles comprises different angles along a surface of a three dimensional shape. 
     
     
         47 . The method of  claim 44 , wherein the jogging of the at least one of the aperture or fiber-optic cable is performed by an electromagnetic actuator that makes small displacement jogs that are less than 70 μm. 
     
     
         48 . A method of  claim 44  further comprising:
 flowing a sample through a flow cell disposed adjacent to the image sensor. 
 
     
     
         49 . The method of  claim 48 , wherein the flow cell is angled with respect to the image sensor. 
     
     
         50 . The method of  claim 48 , wherein the first and one or more different angles lie along an arc that is slightly angled compared to a flow direction and fall within a range between about −89° to +89°.