Patent Abstract:
A method of use for holographic optical traps or gradients in which repetitive cycling of a small number of appropriately designed arrays of traps are used for general and very complex manipulations of particles and volumes of matter. Material transport results from a process resembling peristaltic pumping, with the sequence of holographically-defined trapping or holding manifolds resembling the states of a physical peristaltic pump.

Full Description:
This invention was made with U.S. Government support under Contract No. DMR-9730189 awarded by the National Science Foundation, and through the MRSEC Program of the National Science Foundation under Award No. DMR-9880595. The U.S. Government also has certain rights to the invention pursuant to these contracts and awards. This application is a continuation of U.S. patent application Ser. No. 10/651,370, filed Aug. 29, 2003 now U.S. Pat. No. 6,847,032, which is a continuation of U.S. patent application Ser. No. 09/875,812, filed Jun. 6, 2001, now U.S. Pat. No. 6,639,208. 

   FIELD OF THE INVENTION 
   The present invention is directed generally to a method and apparatus for controlling and manipulating small particles, a movable mass or a deformable structure. More particularly, the present invention is directed to a method and apparatus for using holographic optical traps to control and manipulate particles and volumes of matter in both general and complex ways. 
   BACKGROUND OF THE INVENTION 
   Optical traps use optical gradient forces to trap, most preferably, micrometer-scale volumes of matter in both two and three dimensions. A holographic form of optical trap can use a computer-generated diffractive optical element to create large numbers of optical traps from a single laser beam. These traps can be arranged in any desired configuration dependent on the need at hand. 
   Although systems are known to move particles precisely and with a relatively high degree of confidence, conventional systems require a separate hologram to be projected for each discrete step of a particle&#39;s motion. Computing multiple holograms can be very time consuming and requires substantial computational effort. Furthermore, computer-addressable projection systems required to implement such computer-generated optical traps or other dynamic optical trap systems, such as scanned optical tweezers, tend to be prohibitively expensive. 
   SUMMARY OF THE INVENTION 
   It is therefore an object of the invention to provide an improved method for manipulating particles and volumes of matter in both general and complex methods. 
   It is an additional object of the invention to provide an improved method for moving particles along a predetermined path with a high degree of accuracy and confidence. 
   It is still another object of the invention to provide a method for manipulating particles and volumes of matter which removes the computational burden of achieving complex rearrangements. 
   In accordance with the above objects, projecting a time varying sequence of such trap patterns makes possible dynamic reconfiguration of traps, with each new pattern updating the position of each trap by a distance small enough that particles trapped in the original pattern naturally fall into a corresponding trap in the next. The present invention therefore offers a method for accomplishing complex rearrangements of matter by cycling through a small number of precalculated holographic optical trap patterns. The cycling can be performed mechanically, removing both computational complexity and the expense of a fully general holographic optical trap system. 

   
     BRIEF DESCRIPTION OF THE DRAWINGS 
       FIG. 1  depicts an individual particle being trapped in an optical trap within a manifold of optical traps, wherein the manifold&#39;s position is represented by a dashed line; 
       FIG. 2  shows the transfer of an individual particle from a manifold of traps in a first pattern to a manifold of traps in a second pattern; 
       FIGS. 3A–3D  shows the operative action of an optical peristalsis method; 
       FIG. 4  shows the use of parallel linear manifolds of optical traps for transferring particles along a linear trajectory normal to the manifolds; 
       FIG. 5A  shows curved manifolds directing particles from the periphery of the pattern towards the centers of curvature; and  FIG. 5B  schematically shows how the pattern described in  FIG. 5A  can sweep particles into a channel; 
       FIG. 6A  shows nonuniformly curved manifolds used to divide a flow of particles into two separate flows; and  FIG. 6B  shows nonuniformly curved manifolds to mix two separate flows into a single, larger flow; 
       FIG. 7A  shows a plurality of concentric manifolds transporting particles out of a region; and  FIG. 7B  shows a plurality of concentric manifolds transporting particles into a region; 
       FIG. 8  is a representation of two particles moving in response to an externally applied field and an optical peristalsis pattern; 
       FIG. 9  shows two stages of optical fractionation, with particles of a first type transported to the right and particles of a second type are transported to the left; 
       FIG. 10  is a representation of the implementation of optical peristalsis using dynamical holographic optical traps; 
       FIG. 11  shows a dynamic holographic optical trap system using a transmission-mode computer-addressed spatial light modulator in an optical train; 
       FIG. 12  shows the mechanical cycling of a sequence of static computer-generated diffractive optical elements; 
       FIG. 13  is a representation of a mechanically cycled optical peristalsis system using transmissive computer-generated diffractive optical elements arranged on the periphery of a disc; 
       FIG. 14  shows a plurality of manifolds of optical traps trapping an extended object and rotating the object; and 
       FIG. 15  shows the use of manifolds of optical traps trapping an extended deformable object. 
   

   DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
   Optical peristalsis involves the use of a sequence of pre-calculated holograms projected over time to implement complex redistributions of large numbers of particles over large or selected areas. A key aspect of the invention of optical peristalsis is the non-specific transfer of particles from one manifold of optical traps in a given pattern to the next pattern through the intercession or application of at least two intermediate patterns. The term “pattern” is meant to encompass at least one manifold.  FIG. 1  shows a typical manifold  20  of optical traps  24  arranged in a straight line. Each of the traps  24  is capable of trapping a particle  22  of interest, and the traps  24  are spaced relative to each other so that the particle  22  is unlikely to pass through the manifold  20  without falling into an available one of the traps  24  or being blocked by particles already in the trap  24 . The particle  22  is drawn as a sphere, but could just as easily be irregularly shaped, or even much larger than the separation between the traps  24 . 
   Operation of the optical peristalsis method proceeds by extinguishing the manifold  20  of the traps  24  which frees the particle  22  to move. If another pattern of the traps  24  is illuminated sufficiently nearby, then the particle  22  will be trapped by one (or more) of the traps  24  in the new pattern. In the illustrated case of  FIGS. 3A–3D  a pattern includes two of the manifolds  20  at line  23  and  25 . However, the next pattern could include only one of the manifolds, along line  27  for example. In effect, the particle  22  is thereby transferred from one of the manifolds  20  of the traps  24  in the first pattern  26  to another one of the manifolds  20  in a second pattern  28 . This process is in its simplist form depicted in  FIG. 2 , and shown more generally in  FIGS. 3A–3D . To effect the transfer of the particle  22 , the first pattern  26  can be extinguished first; and then the second pattern  28  is illuminated, provided the interval between the two patterns  26  and  28  is short enough to prevent the trapped particle  22  from “wandering off” (out of the optical gradient) before it can be captured by the next, nearest available trap  24 . Illuminating the second pattern  28  before extinguishing the first pattern  26  also is another operative embodiment, albeit, more complicated to implement. 
   A pattern of the traps can therefore include one or more of the manifolds  20  of discrete the traps  24 , such as discrete tweezers in one embodiment of the invention. Each of the manifolds  20  can include several of the traps  24  arranged along a one-dimensional curve or line, as shown schematically in  FIG. 1 , or also on a two-dimensional surface, or within a three-dimensional volume. The notion of a trapping pattern consisting of a collection of the manifolds  20  is useful for visualizing the process of optical peristalsis. 
     FIG. 3A  shows in further detail one of the particles  22  trapped on one manifold  20  of a particular pattern, labeled as the first pattern  26 . The first pattern comprises two manifolds  50  and  56 . The positions of trapping the manifolds  52  and  54  in the second extinguished pattern  28  (only one manifold for this pattern) and a third extinguished pattern  30  (only one manifold) are also shown. In the first time step, only the first pattern  26  is illuminated. In the next time step represented in  FIG. 3B , the first pattern  26  is extinguished and the second pattern  28  is illuminated. This action transfers the particle  22  from the first manifold  50  of the first pattern  26  to the nearby manifold  52  of the second pattern  28 . In the next time incremental step shown in  FIG. 3C , the second pattern  28  is extinguished and the third pattern  30  is illuminated, thereby transferring the particle  22  again and this time to a manifold  54  on the third pattern  30 . In the final time step as shown in  FIG. 3D , the third pattern  30  is extinguished and the first pattern  26  is illuminated once again. This transfers the particle  22  to the first pattern  26  on the next manifold  56 . Optical peristalsis therefore arises from deterministically transferring the particle  22  from one of the manifolds  20  on a pattern of the optical traps to another of the manifolds  20  on the same second pattern  28  by cycling through a sequence of intermediate patterns. 
   In a most preferred embodiment of the invention, a minimum of three of the patterns  26 ,  28  and  30  are needed to advance the particle  22  deterministically from the one manifold  50  on a trapping pattern to the next manifold  52 . If only two of the equally spaced patterns  26  and  28  were used, the particle  22  could have a substantial probability of either advancing to the next manifold  52  or returning to the initial manifold  50 . In other embodiments, more than the three patterns  26 ,  28  and  30  can be used to transfer a particle  22  in a particular direction. Methods for illuminating and extinguishing the individual manifolds  20  of optical traps  24  are well understood in the art. 
   Repeatedly cycling through the first, second and third patterns  26 ,  28  and  30 , respectively, tends to move the particles  22  from left to right in the arrangement described in  FIG. 3 . Reversing the sequence would drive them right to left. More extensive patterns consisting of more of the manifolds  20  thus can be used to transfer the particles  22  back and forth over the entire field of view of the holographic optical trap system. 
   There are a variety of ways in which optical peristalsis can be used to effect useful rearrangements of collections of the particles  22 . These methods include modifying the shapes of the manifolds  20  within a pattern of the traps  24  by continuous curves. Although a single pattern is described in detail herein, additional intermediate patterns required for transfer between the manifolds  20  would be easily understood and recognized by those skilled in the art. In the examples described herein, the direction of particle flow will be indicated by overlaid arrows. 
     FIG. 4  shows one of the patterns  26  from a linear optical peristaltic pump  33 . Two or more patterns (not shown) interleaved between the manifolds  20  of this pattern  26  can be activated in sequence to drive one or more trapped particles  22  from left to right. Reversing the sequence transfers the particles  22  from right to left. This pattern, and all of the patterns to be described herein, can be oriented in any desired direction 
     FIGS. 5A and 5B  show that patterns consisting of the curved manifolds  20  can be used to concentrate a flow of particles. Conversely, running the same sequence backwards disperses the particles  22 . This capability would be useful for directing the particles  22  out of an open region and into a confined region, such as a reservoir. It is not necessary that the individual manifolds  20  have equal curvature, and varying the curvature can be useful in particular situations. For instance, a linear pumping pattern can be used to sweep the particles  22  into a focusing pattern. The individual spacings between the manifolds  20  also do not have to be equal. Regions of a pattern with more closely spaced forms of the manifolds  20  tend to transfer particles  22  more slowly than regions with more widely spaced ones of the manifolds  20 . The densely packed manifolds  20  tend to concentrate the particles  22  along the direction of motion, while widely spaced manifolds  20  can be used to spread them out. This approach could be particularly beneficial in a focusing pattern to avoid overcrowding the particles  22  as they are concentrated. 
   The distribution and density of the traps  24  along a manifold also can be used to control the flow of the particles  22  between the manifolds  20 . For instance, the traps  24  may be evenly spaced along each of the manifolds  20  and aligned simply from the one manifold  20  to the next and from one pattern to the next. In other embodiments, more complicated arrangements of the traps  24  along the manifolds  20  and between patterns can have uses for controlling the flow of particles  22  along a sequence of patterns. Similarly, varying the intensity, as well as the spacing, of individual traps  24  along the manifolds  20  in a pattern can have useful applications for controlling transport of the particles  22 . 
   The tendency of the shaped manifolds  20  to direct the flow of the particles  22  can also be used to direct the particles  22  into any desired complicated pattern. The example shown in  FIG. 6A  shows the shaped manifolds  20  directing one flow of the particles  22  into two. When run in reverse, such a pattern could be used to combine two (or more) flows into one. Although this may not be as efficient, because the particles  22  from one flow will remain near others from the same flow once the manifolds  20  merge, the methodology can still be used to advantage. 
   The example shown in FIG. of  6 B shows one way to induce mixing of the particles  22  from combined flows. This example shows that the manifolds  20  in a pattern need not be disjoint. The patterns in this systems include a crossed form of the manifolds  20  in the mixing regions. Such crossings can be useful for exchanging the particles  22  between the initially distinct flows. Crossing or otherwise intersecting the simple manifolds  20  to form more complex manifolds  20  introduces a probabilistic element into optical peristalsis. The particles  22  are given a choice of directions to travel near each crossing. Which direction the individual particles  22  choose to follow is determined by random thermal forces at the hand-off from one pattern to the next in a sequence. Hence, the crossings shown in  FIG. 6B  can lead to a certain degree of mixing. 
   A pattern of closed form of the manifolds  20 , such as the example shown in  FIGS. 7A and 7B , can transport the particles  22  into or out of a region. Whether the pattern compacts or rarefies the region depends on the order in which the sequence of patterns is projected. The example in  FIG. 7A  is useful for clearing the particles  22  out of a region, such as to facilitate tests on the suspending fluid or measurements on isolated particles  22 . Such patterns need not be circular, nor need they be confined to the plane. In principle, two-dimensional forms of the manifolds  20  in three-dimensional patterns can be useful for drawing material into a volume, or pushing material out of a volume. 
   Additionally, it should be noted that competition between optical trapping and other external forces can have useful applications. For example, competition between optical trapping and other external forces could be particularly useful in fractionating the particles  22  from a distribution. As an example, it is helpful to consider the particles  22  entrained in a flow of surrounding fluid. Each of the particles  22  is transported by viscous drag in the local flow field ū({overscore (r)}) with a force {overscore (f)}=γū determined by its drag coefficient γ. For a sphere of radius α in a fluid of viscosity η, the drag coefficient is given by γ=6πηα and increases linearly with the particle&#39;s radius. A larger particle feels a greater force when held stationary against a flow than a smaller particle. While the force due to viscous drag is one example of an external force, others such as those due to electric or magnetic fields also would pertain in this embodiment described herein. 
   If the external force is weaker than the optical gradient force of a given one of the optical traps  24 , then the particle  22  being transported by optical peristalsis will move much as described hereinbefore. If the external force is greater than the optical gradient force of the optical trap  24 , then optical peristalsis may only perturb the motion of the particle  22  in the external field. In the idealized example shown in  FIG. 8 , one type of the particle  22  is more strongly attracted to the optical traps  24  than it is driven by the external field. In the example shown in  FIG. 8 , a first particle  60  is more amenable to trapping than a second particle  62  or is less strongly influenced by the external field than the second particle  62 . The first particle  60  is therefore transported by optical peristalsis and can be collected. The second particle  62  is more strongly driven by the external field and passes through the pattern of the traps  24 , perhaps being diverted to a certain extent from its initial course. 
   The two types of the particles  60  and  62  in the example embodiment shown in  FIG. 8  are distinguished either by their affinity for the optical traps  24 , by their response to the external field, or both. Choosing the spatial distribution, strength, and other characteristics of the optical traps  24  in such a pattern makes fractionation of particles possible, with the selectivity determined by the particles&#39; differing physical characteristics. 
   The optical fractionation technique has a number of significant advantages. Fractionation occurs along the direction of the applied field in electrophoresis. Optical fractionation can transport the selected fraction laterally. This means that optical fractionation can operate continuously, rather than on one batch at a time. Because optical fractionation relies on holographic optical trap technology, it can be adapted readily to different fractionation problems. 
   For example, multiple stages of optical fractionation can be applied one after another using the same method and apparatus. Tuning each stage to extract a particular fraction of an initially mixed multicomponent sample then will separate the sample into each of its components, conveniently displacing the sorted components laterally away from the flow, and perhaps transporting them to channels or reservoirs using techniques previously described. 
   The example embodiment shown in  FIG. 9  builds on a single fractionation stage by including a second stage of optical fractionation. The external force driving the particles  22  through the region is directed downward. A first pattern, labeled  80  in  FIG. 9 , selects particles of first type  84  and moves them to the right, diverting, but not collecting particles of second type  86 . The second stage of fractionation, labeled portion  82 , can feature more intense or more closely spaced examples of the traps  24  with the ability to divert particles  22  of the second type  86  away from the external force. As shown, this second stage pattern  82  transports to the left, still further enhancing the separation between the fractions  84  and  86 . Although the two stages of fractionation are presented as conceptually separate, they could be implemented as a single pattern of the optical trap manifolds  20 . This process can also be generalized to include more stages and to incorporate transferring fractionated particles for collection. 
   As discussed above, optical peristalsis works by repetitively cycling through a sequence of trapping patterns. The dynamic holographic systems represented schematically in  FIGS. 10 and 11  are a fully general implementation. In this case, a computer-addressed spatial light modulator  102  creates the configuration of laser beams  104  needed to implement a given pattern of optical traps  114  by encoded the necessary phase modulation onto the wavefront of an input laser beam  100 . In principle, such a system can implement any sequence of trapping patterns, and thus any variant of optical peristalsis. In practice, however, the spatial light modulator  102  has physical limitations such as spatial resolution which limit the complexity of the patterns which they encode. Also, such spatial light modulators  102  tend to be costly. 
   In the embodiment shown in  FIG. 10 , optical peristalsis can be performed with the dynamical holographic optical traps  114 , a typical implementation of which is shown. An input laser beam  100  is reflected off the surface of the computer-addressed spatial light modulator (SLM)  102 . The SLM  102  encodes a computer-generated pattern of phase shifts onto the wavefront of the beam  100 , thereby splitting it into one or more separate laser beams  104 , each emanating from point  107  in the center of the face of the SLM  102 . Lenses  108  and  110  relay each of these laser beams  104  to the conjugate point  112  at the center of the back aperture of a high NA objective lens  112 . This objective lens  112  focuses each of the laser beams  104  into a separate optical trap  114 , only one of which is shown in  FIG. 10  for clarity. A dichroic mirror  116  reflects trapping light into the objective lens  112  while allowing imaging illumination to pass through, thereby permitting images to be formed of the particles being trapped. Updating the phase modulation encoded by the SLM  102  causes a new pattern of the traps  114  to appear. Cycling through a sequence of optical peristalsis patterns in this manner implements the corresponding optical peristalsis process. Because this system can be reconfigured in software, it represents a general implementation of optical peristalsis. In another embodiment shown in  FIG. 11 , the dynamic holographic optical trap system uses a transmission-mode computer-addressed spatial light modulator  200  in an optical train otherwise similar to that in  FIG. 10 . This system also can be used to implement optical peristalsis by cycling through a sequence of trapping patterns. 
   Implementing optical peristalsis does not necessarily require the generality and reconfigurability offered by a dynamic holographic optical trap system. Instead, implementing optical peristalsis preferably uses a holographic optical trap system capable of projecting a (small) sequence of otherwise static patterns. In its simplest preferred form, optical peristalsis can be implemented by mechanically cycling through a sequence of phase patterns to implement a corresponding sequence of holographic optical trapping patterns. One particularly useful embodiment appears in  FIG. 12 . As shown in  FIG. 12 , the phase patterns needed to implement a particular optical peristalsis process are encoded in the surface relief of reflective diffractive optical elements  304 ,  306  and  308 . These elements  304 ,  306 , and  308  are mounted on the face of a prism  300 , and each is rotated into place by a motor  302 . Reversing the motor&#39;s rotation reverses the sequence of patterns and thus the direction of optical peristalsis. Rotating the prism  300  with the motor  302  orients each of the patterns in the input laser beam so that the diffracted beams created by the aligned diffractive optical elements  304 ,  306  and  308  all create optical traps  114 . Stepping the motor  302  through each of the patterns in sequence implements optical peristalsis. Prisms with more than three patterns can be employed, if desired or necessary. 
   Mounting a sequence of fixed reflective diffractive optical elements  304 ,  306  and  308  on the face of a rotating prism  300  can have other uses in holographic optical trap methodologies. Similarly, transmissive diffractive optical elements  404 ,  406 ,  408  and  410  can be located on the periphery of a disk  312  and rotated into the beam  100 , as shown in  FIG. 13 , or into a reflective optical train in sequence. This also has potential applications beyond optical peristalsis. In  FIG. 13 , for example, each of the diffractive optical elements  404 ,  406 ,  408  and  410  is rotated into the optical train to project one pattern of the optical peristalsis sequence. 
   Static reflective or transmissive diffractive optical elements can be fabricated with feature sizes down to the diffraction limit, can have essentially continuous phase encoding, and thus can implement a wider variety of more complicated trapping patterns than can spatial light modulators. Such elements can be produced much more cheaply and do not require a computer to operate. The sequence of patterns in such a system can be changed by changing the prism or disk of diffractive optical elements. In this sense, this implementation is less general than that based on computer-addressed spatial light modulators. 
   Because only a small number of precalculated diffractive optical elements are required to implement optical peristalsis, switchable phase gratings also can be used. The benefits of such an approach include, for example: freedom from moving parts which can drift out of alignment and wear out, the absence of motors which cause vibration and radiate stray electric and magnetic fields, reduction in power requirements and improved compactness. 
   Encoding high-quality phase holograms on film media will allow optical peristalsis to be implemented with the equivalent of film loops. By offering high-speed cycling through large numbers of diffractive optical elements, film-based implementations of holographic optical traps will have applications beyond optical peristalsis. 
   Optical peristalsis also can be useful for particles and other materials such as biological cells which are larger than the physical separation between the traps in an optical peristalsis pattern. Similarly, materials such as proteins, DNA, or molecules could also be manipulated using optical peristalsis. A large object trapped on a “bed of nails” optical trapping pattern still can be moved by translating the bed of nails. Rather than defining a single trapping region, however, an optical peristalsis pattern can establish a large field of traps suitable for immobilizing a large object wherever it is found. Updating the pattern with small displacements, as described above, then will displace the entire object. Potential applications include translating an extended sample into a region where it can undergo tests, rotating the object for examination, or controllably deforming the object. For example, in the embodiment of  FIG. 14 , the manifolds  20  of included optical traps are shown trapping an extended object  80 . Updating the pattern with the manifolds  20  will tend to rotate the extended object  80 . Similarly,  FIG. 15  shows the manifolds  20  of optical traps trapping an extended deformable object  82 . The object  82  is more strongly trapped by denser regions of traps, and moving these regions outward in subsequent patterns tends to stretch the object  82 . 
   Each optical peristalsis sequence performs one specific operation. In some applications, it can be desirable to perform a series of optical peristalsis operations, with the order of the series perhaps depending on the outcome of the preceding operations. For example, optical peristalsis can be used to move a living cell into the center of a microscope&#39;s field of view for reproducible observation. A second sequence then could be engaged to rotate the cell into a desired orientation. Then a third sequence can implement a particular test. Based on the outcome of that test, additional optical peristalsis sequences can be selected to collect the cell or dispose of it. Each of these sequences can be precalculated, thereby removing much of the computational burden from the holographic optical trap system. Similarly, different subsequences of optical peristalsis operations could be incorporated into a single program, wherein a first subsequence could separate particles into two or more distinct flows, a second subsequence could disperse particles from a particular location, a third subsequence could mix two separate streams of particles into a single flow, a fourth subsequence could concentrate a plurality of particles into a particle region, and particles can be “moved” from pattern to pattern in a variety of other ways as well. A variety of combinations of subsequences such as those described herein could be incorporated into a single program, and these subsequences could be used sequentially and/or simultaneously as needed using a variety of types of optical gradients as described herein. Because very few diffractive optical elements are required to implement any one of the sequences, only modest elaboration of the proposed implementations would be needed to select among a collection of available sequences for such multistage operations. 
   Additionally, it is also possible to practice the present invention without the use of optical traps as conventionally understood to require specific optical gradient conditions to hold a particle. For example, a plurality of deterministic optical gradients can be established and incorporated into a plurality of manifolds and patterns as generally described above. These optical deterministic gradients operate to “hold” or restrain, but not necessarily form an optical trap, for individual particles in a particular position for a sufficient period of time in sequence to generate an optical peristalsis effect. In other words, repeatedly cycling through first, second, and third patterns of deterministic optical gradients will move individual particles along a designated path. The optical gradients are deterministic in a sense that the conditions that are applied are sufficient to achieve the intended result with more than just a mere probability of success. 
   While preferred embodiments of the invention have been shown and described, it will be clear to those skilled in the art that various changes and modifications can be made without departing from the invention in its broader aspects as set forth in the claims provided hereinafter.

Technology Classification (CPC): 5