US20050164372A1 - System and method for separating micro-particles - Google Patents

Abstract

A system and method for separating particles is disclosed in which the particles are exposed to a moving light intensity pattern which causes the particles to move at a different velocities based on the physical properties of the particles. This system and method allows particles of similar size and shape to be separated based on differences in the particles dielectric properties.

Description

RELATED APPLICATIONS
• This application is a continuation of application Ser. No. 09/843,902, filed Apr. 27, 2001, which is is related to and claims priority from provisional Application Ser. No. 60/248,451 filed Nov. 13, 2000, which is incorporated by reference as if fully set forth herein.
FIELD OF THE INVENTION
• This invention relates to systems and methods for separating micro-particles and/or nano-particles. More particularly, this invention relates to systems and methods for separating micro-particles and/or nano-particles by using a light source to create a separation force on the particles based on their physical properties.
BACKGROUND OF THE INVENTION
• At the present, there are sorting methods to separate particles, such as cells and other biological entities, based on their size, density, and charge, but none that sort based on optical dielectric properties. For example, laser tweezers have been described that use the interaction of light with a particle to move the particle around. However, in this case, a priori knowledge of which particle to move is required for the tweezers to be used as a sorting mechanism. In other words, tweezers are more of a ‘manipulation and/or transportation’tool, rather than a ‘sorting’ tool. Thus, current methods and systems for separating particles require prior identification of the particles to be separated.
• There is a need for a system and method for separating particles which does not require prior identification of the particles to be separated There is also a need for a system and method for separating particles which does not damage the particles.
SUMMARY OF THE INVENTION
• These needs and others are satisfied by a system and method for separating particles according to the present invention which comprises means for creating a light intensity pattern in the vicinity of the particles and means for moving the light intensity pattern with respect to the particles. The means for creating a light intensity pattern can comprise a light source for producing two light beams aimed to interfere with each other in the vicinity of the two particles.
• In one embodiment, the system comprises a beam splitter and a reflector. In this embodiment, the light source is configured to produce a light beam aimed at the beam splitter. The beam splitter is configured to split the light beam into a first light beam directed toward the particles and a second light beam directed toward the reflector. The reflector is configured to redirect the second light beam toward the particles such that the first and second light beams interfere creating a light intensity pattern in the vicinity of the particles.
• An actuator can be connected to the reflector for moving the reflector to move the light intensity pattern. Alternatively, the actuator can be connected to the light source and beam splitter for moving the light source and beam splitter.
• It is also possible to move the particles relative to the light intensity pattern to create the moving light intensity pattern. In order to do this, the particles can be carried on a slide connected to an actuator configured to move the slide relative to the light intensity pattern.
• The light intensity pattern can also be moved by using a phase modulator to modulate the phase of one of the two light beams with respect to the other. This causes the light intensity pattern created by the interference of the light beams to move spatially. The phase modulator can be place in the path of either the first light beam or second light beam. Alternatively, an amplitude modulator can be used, in which case the interference pattern will move temporally.
• Any material that responds to optical sources may be utilized with these inventions. In the biological realm, examples would include cells, organelles, proteins and DNA, and in the non-biological realm could include metals, semiconductors, insulators, polymers and other inorganic materials.
• Preferably, the light source comprises a laser producing a light beam having a wavelength of between 0.31 μm and 1.8 μm. Using a light beam in this wavelength range minimizes the chance that damage will be caused to the particles if they are living cells or biological entities. Even more preferably, the light beam wavelength range could be 0.8 μm and 1.8 μm. Good, commercially available lasers are available which produce a light beam having a wavelength of 1.55 μm.
• In an alternative embodiment, the system comprises a light source and an optical mask. The light source is configured for producing a light beam directed through the optical mask toward the particles. The optical mask creates a light intensity pattern in the vicinity of the particles. An actuator can be connected to the light source and optical mask for moving the light source and optical mask to create a moving light intensity pattern. Alternatively, the optical mask can be specially configured for producing a moving light intensity pattern in the vicinity of the at least two particles. Another alternative is to include a phase modulator positioned in the light beam path for modulating the phase of the light beam to create a moving light intensity pattern.
• In yet another embodiment the system can comprise a plurality of light sources positioned adjacent to each other for producing a plurality of light beams directed toward the particles The light beams can be aimed to slightly overlap each other to create a light intensity pattern. An actuator can be included for moving the plurality of light sources, thus causing the light intensity pattern to move spatially. Alternatively, the light beams can be dimmed and brightened in a pattern for creating a temporally moving light intensity pattern.
• A method for separating particles according to the present invention comprises the steps of applying a light source to create a light intensity pattern, exposing particles to the light intensity pattern producing force on each particle and moving the light intensity pattern with respect to the particles causing the particles to move with the light intensity pattern at velocities related to their respective physical properties. If the particles have different physical properties they will move at a different velocity causing the particles to separate.
• Preferably, the step of applying a light source comprises interfering at least two optical light beams as discussed herein with respect to one embodiment of a system according to the present invention.
• Alternatively, the step of applying a light source can comprise using an optical mask to create the light intensity pattern. The optical mask can comprise an amplitude mask, a phase mask, a holographic mask, or any other suitable mask for creating a light intensity pattern.
• In another embodiment of a method according to the present invention the step of applying a light source can comprise periodically dimming and brightening a plurality of light sources to create the light intensity pattern.
• Preferably, the light intensity pattern comprises at least two peaks and at least two valleys. The light intensity pattern can be periodic, sinusoidal, nonsinusoidal, constant in time, or varying in time. If the light intensity pattern is periodic, the period can be optimized to create separation between particles.
• In one embodiment, the method comprises moving the light intensity pattern at a constant velocity. The velocity of the light intensity pattern can be optimized to cause separation based on the physical properties of the particles.
• In an alternative embodiment, the method comprises allowing the at least two particles to separate, and then suddenly “jerking” the light intensity pattern to cause particles with different physical properties to fall into different valleys of a potential pattern created by the light intensity pattern.
• The method light intensity pattern can be tuned to a resonant frequency corresponding to the physical properties of one type of particles to optimize separation of that type of particle. The light intensity pattern can be applied in multiple dimensions and the period of the light intensity pattern can be varied in each dimension.
• The particles can be carried in a medium, such as a fluidic medium, which can be either guided or non-guided. If the medium is guided it can include fluidic channels.
• The method can also include superimposing a gradient onto the light intensity pattern. The gradient can be spatially constant or varying and can comprise temperature, pH, viscosity, etc. Additional external forces can also be applied, such as magnetism, electrical forces, gravitational forces, fluidic forces, frictional forces, electromagnetic forces, etc., in a constant or varying fashion.
• A monitoring and/or feedback system can also be included for monitoring the separation between particles and providing feedback information as to separation and location of particles.
• Further object, features and advantages of the present invention will become apparent from the following description and drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
• FIGS. 1A, 1B,2A,2B and3 are block diagrams of various embodiments of a system according to the present invention;
• FIG. 4A is a graphical depiction of an optical grating produced light intensity pattern generated by a system according to the present invention.
• FIG. 4B is a graphical depiction of an energy pattern corresponding to the light intensity pattern ofFIG. 4A.
• FIG. 4C is a graphical depiction of a potential energy pattern corresponding to the light intensity pattern ofFIG. 4A.
• FIGS. 5A, 5B and5C are a graphical depiction of a moving potential energy pattern generated by a system and method according to the present invention.
• FIG. 6 is an enlarged sectional view of a fluidic micro-channel with a graphical depiction of the moving light intensity pattern ofFIG. 4A superimposed in the fluidic micro-channel.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
• In accordance with the present invention, a system and method for separating particles is described that provides distinct advantages when compared to those of the prior art. The invention can best be understood with reference to the accompanying drawing figures.
• Referring now to the drawings, a system according the present invention is generally designated byreference numeral10. Thesystem10 is configured to generate a moving light intensity pattern that produces a force on the particles to be separated. The force causes the particles to move at velocities related to certain physical properties of each particle, such as the particle's optical dielectric constant. Particles with different physical properties will move at different velocities causing the particles to separate based on their physical properties.
• One embodiment of asystem10 according to the present invention is shown inFIG. 1. In this embodiment, thesystem10 comprises alight source12, abeam splitter14, and areflector16. Amotor18 can be connected to thereflector16 for moving or rotating thereflector16. Acontrol system19 is connected to themotor18 for controlling operation of themotor18 and thus movement of thereflector16.
• The particles to be separated can be placed in a medium on aslide22. In one embodiment of the invention, theslide22 includes a non-guided fluidic medium, such as water. In another embodiment, shown inFIG. 6, theslide22 includesfluidic channels500,502 and504 through which theparticles410,412 travel.
• The medium can be non-guided or guided. One example of a guided medium is a medium comprising fluidic channels as is well known in the art.
• Thelight source12 is positioned to produce alight beam24 that is aimed at thebeam splitter14. Thebeam splitter14 splits thelight beam24 into twolight beams26,28 and directs one of the light beams26 toward thereflector16 and theother light beam28 toward theslide22. Thereflector16 redirects lightbeam26 toward theslide22. The light beams26,28 are focused near the particles and aimed to interfere with each other to create a light intensity pattern near the particles.
• Themotor18 can be used to move or rotate thereflector16, which causes the light intensity pattern to move in space. Acontrol system19 is connected to themotor18 to control operation of themotor18. By moving the light intensity pattern in space and keeping theslide22 fixed, forces created on the particles by the light intensity pattern cause the particles to move at velocities related to each particle's physical properties as described herein. The particles can also be caused to move by fixing the light intensity pattern in space and mechanically moving theslide22 carrying the particles. This causes the light intensity pattern to move in space relative to the particles.
• Alternatively,motor18 can be connected to thelight source12 andbeam splitter14. In this embodiment thelight source12 andbeam slitter14 can be moved or rotated by themotor18. This causeslight beam28 to move relative tolight beam26, which, in turn, causes the light intensity pattern to move.
• In another embodiment, shown inFIG. 1B, the light intensity pattern is moved by modulating the relative phase of the light beams26,28. In this embodiment, aphase modulator20 is positioned in the path oflight beam26. Thephase modulator20 is configured to modulate the phase oflight beam26 relative to the phase oflight beam28. Acontrol system19 is connected to thephase modulator20 for controlling operation of thephase modulator20. Alternatively, thephase modulator20 can be positioned in the path oflight beam28 for modulating the phase oflight beam28 relative to the phase oflight beam26.
• Modulating the phases oflight beams26 and28 relative to each other causes the light intensity pattern created by the interference oflight beams26 and28 to move. Moving the light intensity pattern relative to the particles creates forces on the particles related to the physical properties of each particle. As described above, these forces will cause particles with different physical properties to move at different relative velocities.
• Alternatively, an amplitude modulator can be used instead of thephase modulator20. The amplitude modulator can be used for modulating the amplitude of the light beams24,26,28 thus creating a moving light intensity pattern.
• Preferably, thelight source12 comprises a laser for producinglight beams26 and28 coherent with respect to each other. Alternatively, two light sources could be used to producelight beams26 and28.
• In applications where the particles are biological material or living cells, it is preferable that the laserproduce light beams26,28 having a wavelength of between 0.3 μm and 1.8 μm so as not to generate excessive heat that could damage the particles. More preferably, the laser would producelight beams26,28 having a wavelength of greater than 0.8 μm. Very good lasers are commercially available which producelight beams26,28 having a wavelength of 1.55 μm and would be appropriate for use in asystem10 according to the present invention. Alternatively, thelight source12 can produce incoherent light beams26,28.
• In another embodiment of the invention, shown inFIG. 2A, the system110 comprises alight source112 and anoptical mask114. Amotor116 can be connected to thelight source112 andoptical mask114 for moving or rotating thelight source112 andoptical mask114. Acontrol system119 is connected to themotor116 for controlling operation of themotor116 and thus movement of thelight source112 andoptical mask114. In this embodiment, thelight source112 produces alight beam118 that is aimed through theoptical mask114 toward aslide120 holding the particles to be separated.
• Theoptical mask114 is configured to create a light intensity pattern near the particles. Themotor116 can be used to move or rotate thelight source112 andoptical mask114 thus causing the light intensity pattern to move. Alternatively, the light intensity pattern can be fixed in space and theslide120 can be moved producing relative motion between the light intensity pattern and the particles.
• Theoptical mask114 can comprise an optical phase mask, an optical amplitude mask, a holographic mask or any similar mask or device for creating a light intensity pattern. In another alternative embodiment, theoptical mask114 can be specially configured to produce a moving light intensity pattern. This type ofoptical mask114 can be produced by writing on the mask with at least two light beams. In essence, one light beam writes on the mask to create the light intensity pattern and the other mask erases the mask. In this embodiment, a new light intensity pattern is created each time the mask is written upon.
• In the embodiment shown inFIG. 2B, aphase modulator122 is used to create the moving light intensity pattern. Thephase modulator122 is positioned between thelight source112 and theoptical mask114 such thatlight beam118 is directed through thephase modulator112. Acontrol system119 is connected to thephase modulator122 for controlling operation of thephase modulator112.
• In yet another embodiment, shown inFIG. 3, thesystem10 comprises a plurality oflight sources212 positioned adjacent to each other such that they producelight beams214 directed toward aslide216 holding the particles to be separated. In one embodiment, thelight sources212 are aimed to createlight beams214 that overlap each other to produce a light intensity pattern.
• Anactuator218 can be attached to thelight sources212 for moving or rotating thelight sources212 to move the light intensity pattern with respect to theslide216. Acontrol system219 is connected to theactuator218 for controlling operation of theactuator218. For example, motors (not shown) can be attached to each of thelight sources212. The light intensity pattern can also be moved relative to theslide216 by modulating phase, moving theslide216 relative to thelight sources212 or in any other described herein.
• Alternatively, thelight sources212 can be aimed such that thelight beams214 slightly overlap each other near theslide216. A light intensity pattern can be created by switching the light sources to be dimmed and brightened in certain patterns to give the appearance of a moving light intensity pattern. For example, in one embodiment thelight sources212 are dimmed and brightened such that at any given moment in time, whenever one light source is bright, all adjacent light sources are dim and when the first light source is dim the adjacent light sources are bright.
• In operation, focusing a light beam in the vicinity of a particle causes the light beam to interact with optical dipoles inside the particle. Maximum intensity of a light beam is achieved at the focal point of the beam. The particle tends to move toward the point of maximum intensity of the light beam because the minimum energy for the overall system is achieved when the dipoles of the particle reside where the maximum intensity of the light beam occurs.
• A system according to the present invention, such as those described infra, are configured to create a variable light intensity pattern.FIGS. 4A, 4B, and4C show a periodiclight intensity pattern400, theforce402 exerted on a particle by thelight intensity pattern400, and the potential404 exerted on a particle by thelight intensity pattern400, respectively. Thelight intensity pattern400 shown inFIG. 4A is sometimes referred to as an optical grating.
• Particles subjected to thelight intensity pattern400 ofFIG. 4A tend to move toward the peak intensity points406. Thewells408 of thepotential pattern404 shown inFIG. 4C represent points where the overall system energy is at a minimum. Thus, a particle will tend to move toward thewells408 of thepotential pattern404.
• Light intensity patterns400 created according to the present invention can comprise at least twopeaks406 and at least twovalleys407. Suitablelight intensity patterns400 can be periodic, sinusoidal, nonsinusoidal, constant in time or varying in time. If thelight intensity pattern400 is periodic, the period can be optimized to create separation between particles exposed to thelight intensity pattern400. For example, for large particles the period length can be increased to increase the size ofwells408 in the correspondingpotential pattern404 to accommodate the large particles.
• FIGS. 5A, 5B and5C show twoparticles410,412 exposed to apotential pattern406. In this figure,particles410 and412 are of similar size and shape but have different dielectric constants.
• As described infra, moving thelight intensity pattern400 and consequently the potential406 created by thelight intensity pattern400, relative toparticles410,412 exposed to thelight intensity pattern400 causes theparticles410,412 to move at velocities related to the physical properties of theparticles410,412. For example, the force acting on a particle is proportional to the dielectric constant of the particle. More specifically, the force is proportional to (E_p−E_m)/(E_p+2 E_m). Thus, twoparticles410,412 of similar size and shape having different dielectric properties will travel at different velocities when exposed to a movinglight intensity pattern400.
• The potential406 created by thelight intensity pattern400 causes theparticles410,412 to move towardwells408 in thepotential pattern406. Because thelight intensity pattern400, and consequently thepotential pattern406, are moving, theparticles410,412 “surf” on waves created in thepotential pattern406. The waves includepeaks414 of high potential andwells408 of low potential.
• Theparticles410,412 move with thepotential pattern406 at velocities related to theparticles410,412 physical properties. One such physical property is the dielectric constant of theparticles410,412. Because the dielectric constants ofparticles410 and412 are different, they will move at different velocities when exposed to thepotential pattern406 created by thelight intensity pattern400.
• In one embodiment, thelight intensity pattern400, and consequently thepotential pattern406, is moved at a constant velocity. The velocity can be optimized to cause separation of theparticles410,412 based on the particles'410,412 physical properties. For example, a maximum velocity exists for eachparticle410,412 such that if the maximum velocity is exceeded, thepeak414 on which theparticle410 or412 is “surfing” will pass theparticle410 or412 causing theparticle410 or412 to fall into the preceding well408.
• In this embodiment, a velocity is chosen between the maximum velocities ofparticles410 and412. Assuming the maximum velocity ofparticle412 is higher than the maximum velocity ofparticle410, when exposed to thepotential pattern406 shown inFIG. 5A,particle412 will “surf” onpeak414 andparticle410 will fall behind into well408 thus separatingparticles410 and412 based on their physical properties.
• In another embodiment is shown inFIGS. 5B and 5C. In this embodiment,particles410 and412 are exposed topotential pattern406 for a predetermined amount of time to allow theparticles410,412 to separate slightly as shown inFIG. 5B. Once theparticles410,412 have separated slightly, thepotential pattern406 is “jerked” forward a predetermined difference such that theparticles410,412 are positioned on opposites sides ofpeak414. Once the particles are positioned on opposite sides ofpeak414, the forces exerted on theparticles410,412 cause them to fall intowells408 on opposite sides ofpeak414 thus separating theparticles410 and412 based on their physical properties.
• In one application of the invention, shown inFIG. 6, a movinglight intensity pattern400 can be superimposed onto a fluidic channel guided medium506 havingfluidic channels500,502 and504. Thechannels500,502 and504 are arranged in a T-shape with thelight intensity pattern400 being superimposed on the branch of the “T” (i.e. the junction betweenchannels500,502, and504).
• Theparticles410,412 travel fromchannel500 into thelight intensity pattern400. Thelight intensity pattern400 is configured to moveparticles410 and412 in different directions, as described infra, based on the particles'410,412 physical properties. In this case, thelight intensity pattern400 is configured to moveparticle412 intochannel502 andparticle410 intochannel504. In this manner, theparticles410,412 can be separated and collected from theircorresponding channels504,502, respectively.
• Using an application such as this, the light intensity pattern can be configured to moveparticles410 having a physical property below a certain threshold into onechannel504 andparticles412 having a physical property above the threshold into theother channel502. Thus, various particles can be run throughchannel500 and separated based on a certain threshold physical property. Multiple fluidic channel guidedmediums500 can be connected tochannels502 and/or504 to further sort the separatedparticles410,412 based on other threshold physical properties.
• Additional optimization can be done to facilitate particle sorting. For example, eachparticle410,412 has a specific resonant frequency. Tuning the wavelength of thelight intensity pattern400 to the resonant frequency of one of theparticles410 or412 increases the force exerted on thatparticle410 or412. If, for example, the frequency of the light intensity pattern is tuned to the resonant frequency ofparticle412, the velocity at whichparticle412 travels is increases, thus increasing the separation betweenparticles410 and412.
• Other forces can also be superimposed onto theparticles410,412 to take advantage of additional differences in the physical properties of theparticles410,412. For example, a gradient, such as temperature, pH, viscosity, etc., can be superimposed onto theparticles410,412 in either a linear or non-linear fashion. External forces, such as magnetism, electrical forces, gravitational forces, fluidic forces, frictional forces, electromagnetic forces, etc., can also be superimposed onto theparticles410,412 in either a linear or non-linear fashion.
• Thelight intensity pattern400 and/or additional forces can be applied in multiple dimensions (2D, 3D, etc.) to furtherseparate particles410,412. The period of thelight intensity pattern400 can be varied in any or all dimensions and the additional forces can be applied linearly or non-linearly in different dimensions.
• A monitoring system, not shown, can also be included for tracking the separation of theparticles410,412. The monitoring system can provide feedback to the system and the feedback can be used to optimize separation or for manipulation of theparticles410,412.
• It will be apparent to those skilled in the art that modifications may be made without departing from the spirit and scope of the invention. Accordingly, it is not intended that the invention be limited except as may be necessary in view of the appended claims.

Claims (19)

1. A system for separating at least two particles, the particles having different physical properties, the system comprising:

means for creating a light intensity pattern in the vicinity of the at least two particles; and

means for moving the light intensity pattern with respect to the at least two particles.

2. The system according toclaim 1, wherein the means for creating a light intensity pattern comprises a light source for producing two light beams aimed to interfere with each other in the vicinity of the at least two particles.

3. The system according toclaim 2, wherein the light beams comprise coherent light beams.

4. The system according toclaim 1, further comprising a beam splitter and a reflector, wherein the light source is configured to produce a light beam aimed at the beam splitter, the beam splitter is configured to split the light beam into a first light beam directed toward the at least two particles and a second light beam directed toward the reflector, the reflector is configured to redirect the second light beam toward the at least two particles such that the first and second light beams interfere creating a light intensity pattern in the vicinity of the at least two particles.

5. The system according toclaim 4, wherein the means for moving comprises an actuator connected to the reflector for moving the reflector.

6. The system according toclaim 4, wherein the means for moving comprises an actuator connected to the light source and beam splitter for moving the light source and beam splitter.

7. The system according toclaim 2, wherein the means for moving is configured to move the light intensity pattern in space.

8. The system according toclaim 2, wherein the means for moving is configured to move the light intensity pattern in time.

9. The system according toclaim 2, wherein the means for moving is configured to fix the light intensity pattern and move the at least two particles in space relative to the light intensity pattern.

10. The system according toclaim 9 wherein the at least two particles are held on a slide and the means for moving comprises an actuator for moving the slide relative to the light intensity pattern.

11. The system ofclaim 2 wherein the means for moving comprises a phase modulator for modulating the phase of one of the two light beams with respect the other.

12. The system ofclaim 2 wherein the light source comprises a laser.

13. The system ofclaim 2 wherein the light beam is between 0.31 μm and 1.8 μm.

14. The system ofclaim 2 wherein the light beam is between 0.8 μm and 1.8 μm.

15. The system ofclaim 2 wherein the light beam has a wavelength of 1.55 μm.

16. The system ofclaim 1 wherein the means for creating a light intensity pattern comprises a light source and an optical mask, which can be a phase mask, an amplitude mask, or a holographic mask, the light source being configured for producing a light beam directed through the optical mask toward the at least two particles.

17. The system ofclaim 1 further comprising a plurality of light sources positioned adjacent to each other for producing a plurality of light beams directed toward the at least two particles for creating a light intensity pattern.

18. The system ofclaim 17 further comprising an actuator for moving the plurality of light sources.

19. The system ofclaim 17 wherein the plurality of light beams are aimed to slightly overlap each adjacent light beam in the vicinity of the at least two particles, the plurality of light sources being configured to be dimmed and brightened in a pattern for creating a moving light intensity pattern.

Images