Methods and apparatus for use of optical forces for identification, characterization and/or sorting of particles

Abstract

Apparatus and methods are provided for interacting light with particles, including but not limited to biological matter such as cells, in unique and highly useful ways. Optophoresis consists of subjecting particles to various optical forces, especially optical gradient forces, and more particularly moving optical gradient forces, so as to obtain useful results. In biology, this technology represents a practical approach to probing the inner workings of a living cell, preferably without any dyes, labels or other markers. In one aspect, a particle may be characterized by determining its optophoretic constant or signature. For example, a diseased cell has a different optophoretic constant from a healthy cell, thereby providing information, or the basis for sorting. In the event of physical sorting, various forces may be used for separation, including fluidic forces, such as through the use of laminar flow, or optical forces, or mechanical forces, such as through adhesion. Various techniques for measuring the dielectric constant of particles are provided.

We claim:  
     
         1 . A method for the characterization of a particle comprising the steps of: 
 observing a first physical position of a particle,    optically illuminating the particle to subject it to an optical force,    observing the second physical position of the particle, and characterizing the particle based at least in part upon reaction of the particle to the optical force.    
     
     
         2 . The method of  claim 1  wherein the optical illumination includes an optical gradient field.  
     
     
         3 . The method of  claim 2  wherein the optical gradient field is a moving optical gradient field.  
     
     
         4 . The method of  claim 1  wherein the optical illumination includes an optical scattering force field.  
     
     
         5 . The method of  claim 1  wherein the optical illumination includes a moving optical gradient force field and another force.  
     
     
         6 . The method of  claim 1  wherein the first position and second position are different.  
     
     
         7 . The method of  claim 1  wherein the positions are the same.  
     
     
         8 . The method of  claim 7  wherein the characterization includes non-movement as indicative of the state.  
     
     
         9 . The method of  claim 7  wherein the characterization includes a non-positional parameter.  
     
     
         10 . The method of  claim 9  wherein the non-positional parameter is rotation of the particle.  
     
     
         11 . The method of  claim 1  wherein the characterization involves a comparison of the first position and the second position.  
     
     
         12 . The method of  claim 6  wherein the amount of difference of movement indicates a characterization state.  
     
     
         13 . The method of  claim 6  wherein the direction of movement is indicative of a characterization state.  
     
     
         14 . The method of  claim 1  wherein the characterization utilizes the optophoretic constant of the particle.  
     
     
         15 . The method of  claim 1  wherein the characterization utilizes the optophoretic signature of the particle.  
     
     
         16 . A method for analyzing particles comprising the steps of: 
 electrokinetically moving the particles, and    subjecting the particles to optical forces for sorting.    
     
     
         17 . The method of  claim 6  wherein the optical force is an optical gradient force.  
     
     
         18 . The method of  claim 6  wherein the optical force is a moving optical gradient field.  
     
     
         19 . The method of  claim 6  wherein the optical force is an optical scattering force.  
     
     
         20 . The method of  claim 6  wherein the electrokinetic force is an electrophoretic force.  
     
     
         21 . The method of  claim 6  wherein the electrokinetic force is a dielectrophoretic force.  
     
     
         22 . The method of  claim 6  wherein the electrokinetic force is an electroosmotic force.  
     
     
         23 . A method for separating particles comprising the steps of: 
 subjecting particles to optical gradient force,    analyzing where information comes merely from the fact that particle moved, or moved in a particular way, and    separating desired particle from other particles.    
     
     
         24 . The method of  claim 14  wherein the separation is fluidic.  
     
     
         25 . The method of  claim 14  wherein the separation is mechanical.  
     
     
         26 . The method of  claim 16  wherein the mechanical separation utilizes a capture structure.  
     
     
         27 . The method of  claim 14  wherein the separation is optical.  
     
     
         28 . The method of  claim 18  wherein the optical separation uses an optical tweezer.  
     
     
         29 . The method of  claim 18  wherein the optical separation uses an optical gradient force.  
     
     
         30 . The method of  claim 18  wherein the optical separation uses an optical scattering force.  
     
     
         31 . A method for determining the dielectric constant of a particle comprising the steps of: 
 subjecting the particle to an optical gradient force in a plurality of media having different dielectric constants,    monitoring the motion of the particle when subject to the optical gradient force in the various media, and    determining the dielectric constant of the particle based upon the relative motion in the various media.    
     
     
         32 . The method of  claim 22  wherein the media are in different vessels.  
     
     
         33 . The method of  claim 22  wherein the media gradient is in one vessel.  
     
     
         34 . The method of  claim 24  wherein the vessel is a tube.  
     
     
         35 . The method of  claim 25  wherein the tube has a gradient of dielectric constant along its length.  
     
     
         36 . A method for separating particles according to size comprising the steps of. 
 subjecting the particles to a optical fringe pattern,    moving the fringes relative to the particles,    wherein the improvement comprises selecting the period of the fringes to have a differential effect on differently sized particles.    
     
     
         37 . The method of  claim 27  wherein certain of the particles are smaller than the period and certain of the particles are larger than the period.  
     
     
         38 . The method of  claim 28  wherein the larger particles are larger than the fringe period.  
     
     
         39 . A method for separating particles based upon flexibility, comprising the steps of: 
 subjecting the particles to an optical pattern having fringes, the fringe spacing being less than the size of the particle in an uncompressed state,    moving the fringes relative to the medium containing the particles, and    whereby particles having relatively higher flexibility are separated from those with relatively lower flexibility.    
     
     
         40 . A method for separating particles comprising the steps of: 
 providing one or more particles,    subjecting particles to light so as to cause a scattering force on the particles, and    separating the particles based upon the reaction to at least the scattering force.    
     
     
         41 . A method for separating particles comprising the steps of: 
 determining first positions of two or more particles,    subjecting the particles to an optical gradient force to effect relative motion of the particles,    determining second positions of the particles, and    selectively removing a subset of the particles based upon a force other than the gradient force.    
     
     
         42 . A method for separating particles having different dielectric constants comprising the steps of: 
 separating the particles in a medium having a dielectric constant chosen to enhance the sensitivity of the discrimination between the particles, and    changing the medium to one having a dielectric constant which causes faster separation between the particles.    
     
     
         43 . The method for separating particles of claim  42  wherein the sensitivity is enhanced by utilizing a medium having a dielectric constant which is closer to one species of particle than the other.