Systems, devices and methods for three-dimensional imaging of moving particles

Abstract

Disclosed are methods, devices, systems and applications for camera-less, high-throughput three-dimensional imaging of particles in motion. In some aspects, a system includes a particle motion device to allow particles to move along a travel path; an optical illumination system to produce an asymmetric illumination area of light in a region of the travel path of a particle that scans over a plurality of sections of the particle at multiple time points while the particle is moving; an optical detection system optically interfaced with the particle motion device to obtain optical signal data associated with different parts of the particle corresponding to the particle's volume during motion in the travel path; and a data processing unit to process the optical signal data obtained by the optical detection system and produce data including information indicative of 3D features of the particle.

What is claimed is: 
     
         1 . A system for imaging a moving particle, comprising:
 a light source emitting a light beam;   a light redirection device to modulate the light beam to produce an illumination area that is repeatedly swept across an interrogation area where the moving particle travels through, thereby producing an optical signal when the illumination area illuminates the moving particle;   a spatial filter to allow portions of the optical signal to pass through, thereby generating a filtered optical signal corresponding to a section of the moving particle; and   a light detection device for detecting the filtered optical signal.   
     
     
         2 . The system of  claim 1 , wherein the light redirection device comprises an acousto-optic deflector. 
     
     
         3 . The system of  claim 2 , wherein the acousto-optic deflector generates a periodic angle change at a rate of 100 kHz to 1 MHz. 
     
     
         4 . The system of  claim 2 , wherein the acousto-optic deflector produces a deflected first-order beam at a different angle for each frequency. 
     
     
         5 . The system of  claim 2 , wherein the filtered optical signal detected by the light detection device is synchronized with a reference output of a tuning voltage of a driver for the acoustic-optic deflector. 
     
     
         6 . The system of  claim 1 , wherein the illumination area comprises an asymmetric illumination area comprising one dimension of illumination thinner than another dimension of illumination to form a shape like an illumination plane. 
     
     
         7 . The system of  claim 6 , wherein the illumination area is swept across the interrogation area in a direction approximately perpendicular to the illumination plane. 
     
     
         8 . The system of  claim 1 , wherein the light redirection device produces an asymmetric intensity profile. 
     
     
         9 . The system of  claim 1 , wherein the interrogation area comprises a fluidic channel of a flow cell. 
     
     
         10 . The system of  claim 9 , wherein the flow cell comprises a sheath flow and sample flow. 
     
     
         11 . The system of  claim 9 , wherein the flow cell comprises a flow rate of about 10 centimeters per second to 20 centimeters per second. 
     
     
         12 . The system of  claim 1 , wherein the system is operable to produce image data of a plurality of moving particles at a throughput of 500 particles per second. 
     
     
         13 . The system of  claim 1 , further comprising a particle motion device. 
     
     
         14 . The system of  claim 13 , wherein the particle motion device comprises a substrate, wherein a particle is fixed to the substrate and the substrate is moveable by a positioning system, thereby providing the moving particle. 
     
     
         15 . The system of  claim 1 , wherein the filtered optical signal comprises a one-dimensional data point corresponding to a time point. 
     
     
         16 . The system of  claim 15 , wherein signals outside a specific area or a specific time point are blocked by the spatial filter. 
     
     
         17 . The system of  claim 1 , wherein the optical illumination system is configured to scan, while the moving particle is moving in a first direction, a first section of the moving particle in a first plane at a first time point and to scan a second section of the moving particle in a second plane at a second time point, thereby producing a temporal signal that spatially maps to the moving particle. 
     
     
         18 . The system of  claim 1 , further comprising a data processing unit in communication with the light detection device, wherein the light detection device converts the filtered optical signal into filtered optical signal data, and wherein the data processing unit includes a processor configured to process the filtered optical signal data obtained by the light detection device and produce data including information indicative of three dimensional features of the moving particle. 
     
     
         19 . The system of  claim 1 , wherein the spatial filter comprises a plurality of apertures. 
     
     
         20 . A method of imaging a moving particle, comprising:
 emitting a light beam from a light source;   modulating the light beam to produce an illumination area, wherein the modulating the light beam includes repeatedly sweeping the illumination area across an interrogation area which the moving particle travels through, thereby producing an optical signal when the illumination area illuminates the moving particle;   filtering portions of the optical signal, thereby generating a filtered optical signal corresponding to a section of the moving particle; and   detecting the filtered optical signal.   
     
     
         21 . The method of  claim 20 , further comprising construing a volume of the moving particle from the filtered optical signal. 
     
     
         22 . A system for imaging a moving particle, comprising:
 a light source to emit a light beam, wherein the light beam illuminates an asymmetric area with a first dimension much wider than a second dimension of the illuminated area;   a light beam modulation device to modify the light beam to illuminate different parts of the moving particle at different times, thereby producing an optical signal related to the properties of the moving particle;   a spatial filter comprised of one or more apertures to allow portions of the optical signal to enter an optical detector, thereby generating a spatially filtered optical signal corresponding to a section of the moving particle;   a light detection device to detect the spatially filtered optical signal and output a detected signal; and   a signal processing unit to process the detected signal and display the detected signal as an image of the moving particle.   
     
     
         23 . A system for imaging a moving particle, comprising:
 a light source to emit a light beam, wherein the light beam illuminates an asymmetric area with a first dimension much wider than a second dimension of the illuminated area;   a light beam modulation device to modify the light beam to illuminate different parts of the moving particle at different times, thereby producing an optical signal related to properties of the moving particle;   a spatial filter to allow portions of the optical signal to enter a light detection device, thereby generating a spatially filtered optical signal corresponding to a section of the moving particle; and   a signal processing unit to apply an algorithm to transform a temporal signal from the light detection device into an image of the moving particle.   
     
     
         24 . A method of imaging a moving particle, comprising:
 emitting a light beam from a light source, wherein the light beam illuminates an asymmetric area with a first dimension much wider than a second dimension of the illuminated area;   modulating the light beam to illuminate different parts of the moving particle at different times, thereby producing an optical signal related to the properties of the moving particle;   filtering portions of the optical signal, thereby generating a filtered optical signal corresponding to a section of the moving particle;   detecting the filtered optical signal;   processing the filtered optical signal to generate a detected signal; and   displaying the detected signal as an image of the moving particle.