Optical switching and sorting of biological samples and...

Optical waveguides – With optical coupler – Switch

Reexamination Certificate

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C428S188000, C422S105000

Reexamination Certificate

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06778724

ABSTRACT:

BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention generally concerns optical tweezers, microfluidics, flow cytometry, biological Micro Optical Electro Mechanical Systems (Bio-MOEMS), Laguerre-Gaussian mode emissions from Vertical Cavity Surface Emitting Lasers (VCSELs), cell cytometry and microfluidic switches and switching.
The present invention particularly concerns the sorting of microparticles in fluid, thus a “microfluidic sorting device”; and also the directed movement, particularly for purposes of switching, of microparticles based on the transference of momentum from photons impinging on the microparticles, ergo “photonic momentum transfer”.
2. Description of the Prior Art
2.1 Background to the Functionality of the Present Invention
In the last several years much attention has been paid to the potential for lab-on-a-chip devices to significantly enhance the speed of biological and medical research and discovery. See P. Swanson, R. Gelbart, E. Atlas. L. Yang, T. Grogan, W. F. Butler, D. E. Ackley, and C. Sheldon. “A fully multiplexed CMOS biochip for DNA analysis,” Sensors and Actuators B 64, 22-30 (2000). See also M. Ozkan, C. S. Ozkan, M. M. Wang, O. Kibar, S. Bhatia, and S. C. Esener, “Heterogeneous Integration of Biological Species and Inorganic Objects by Electrokinetic Movement,” IEEE Engineering in Medicine and Biology, in press.
The advantages of such bio-chips that have been demonstrated so far include the abilities to operate with extremely small sample volumes (on the order of nanoliters) and to perform analyses at much higher rates than can be achieved by traditional methods. Devices for study of objects as small as DNA molecules to as large as living cells have been demonstrated. See P. C. H. Li and D J, Harrison, Transport, Manipulation, and Reaction of Biological Cells On-Chip Using Electrokinetic Effects,” Anal. Chem. 69, 1564-1569 (1997).
One important capability for cell research is the ability to perform cell sorting, or cytometry, based on the type, size, or function of a cell. Recent approaches to micro-cytometry have been based on electrophoretic or electro-osmotic separation of different cell types. See A. Y. Fu, C. Spence, A. Scherer, F. H. Arnold, and S. R Quake, “A microfabricated fluorescence-activated cell sorter,” Nature 17.1109-1111 (1999).
2.2 Scientific Background to the Structure of the Device of the Present Invention
The present invention will be seen to employ optical tweezers. See A. Ashkin, J. M. Dziedzic, J. E. Bjorkholm, and S. Chu, “Observation of a single-beam gradient force optical trap for dielectric particles;” Opt. Lett. 11, 288-291) (1986).
The present invention will also be seen to employ micro-fabricated fluidic channels. See H. -P. Chou, C. Spence. A. Scherer. and S. Quake, “A microfabricated device for sizing and sorting DNA molecules,” Proc. Natl. Acad. Sci. USA 96 11-13 (1999).
In previous demonstrations of the optical manipulation of objects through defined fluidic channels, photonic pressure was used to transport cells over the length of the channels. See T. N. Buican M. J. Smyth, H. A. Crissman, G. C. Salzman, C. C. Stewart, and J. C. Martin, “Automated single-cell manipulation and sorting by light trapping.” Appl. Opt, 26, 3311-5316 (1987). The device of the present invention will be seen to function oppositely.
2.3 Engineering, and Patent, Background to the Structure of the Device of the Present Invention
There are many existing (i) bio-chip (lab-on-a-chip) technologies, and (ii) microfluidic technologies. Most of these technologies use electrical or mechanical force to perform switching within the channels. The present invention is unique in that optics (as generate photonic pressure, or radiation pressure) is used to perform switching—particularly of small particles flowing in microfluidic channels.
2.3.1 Background Patents Generally Concerning Optical Tweezing and Optical Particle Manipulation
The concept of using photonic pressure to move small particles is known. The following patents, all to Ashkin, generally deal with Optical Tweezers. They all describe the use of optical “pushing” and optical “trapping” forces, both of which are used in the present invention. These patents do not, however, teach or suggest such use of optical forces in combination with microfluidics as will be seen to be the essence of the present invention.
U.S. Pat. No. 3,710,279 to Askin, assigned to Bell Telephone Laboratories, Inc. (Murray Hill, N.J.), for APPARATUSES FOR TRAPPING AND ACCELERATING NEUTRAL PARTICLES concerns a variety apparatus for controlling by radiation pressure the motion of particle, such as a neutral biological particle, free to move with respect to its environment. A subsequent Askin patent resulting from a continuation-in-part application is U.S. Pat. No. 3,808,550.
Finally, U.S. Pat. No. 4,893,886 again to Ashkin, et al., assigned to American Telephone and Telegraph Company (New York, N.Y.) and AT&T Bell Laboratories (Murray Hill, N.J.), for a NON-DESTRUCTIVE OPTICAL TRAP FOR BIOLOGICAL PARTICLES AND METHOD OF DOING SAME, concerns biological particles successfully trapped in a single-beam gradient force trap by use of an infrared laser. The high numerical aperture lens objective in the trap is also used for simultaneous viewing. Several modes of trapping operation are presented.
2.3.2 Patents Showing Various Conjunctions of Optical Tweezing/Optical Manipulation and Microfluidics/Microchannels
U.S. Pat. No. 4,887,721 to Martin, et al., assigned to Bell Telephone Laboratories, Inc. (Murray Hill, N.J.), for a LASER PARTICLE SORTER, concerns a method and apparatus for sorting particles, such as biological particles. A first laser defines an optical path having an intensity gradient which is effective to propel the particles along the path but which is sufficiently weak that the particles are not trapped in an axial direction. A probe laser beam interrogates the particles to identify predetermined phenotypical characteristics of the particles. A second laser beam intersects the driving first laser beam, wherein the second laser beam is activated by an output signal indicative of a predetermined characteristic. The second laser beam is switchable between a first intensity and a second intensity, where the first intensity is effective to displace selected particles from the driving laser beam and the second intensity is effective to propel selected particles along the deflection laser beam. The selected particles may then be propelled by the deflection beam to a location effective for further analysis.
The described particle propulsion means of Martin, et al. concerns (i) the suspension of particles by fluidics and (ii) the use of an optical pushing beam to move particles around in a cavity. The application of sorting—as is performed by certain apparatus of the present invention—is also described. However, the present invention is distinguished over U.S. Pat. No. 4,887,721 for SORTING IN MICROFLUIDICS to Martin, et al. because this patent teaches the use of optical beams to do all particle transport, while the present invention uses optical beams only for switching, with transport accomplished by microfluidic flow. In the apparatus of U.S. Pat. No. 4,887,721 a single beam pushes a particle along from one chamber to the next. It will soon be seen that in the various apparatus of the present invention continuous water flow serves to move the particles around, and optics is only used as the switch. This is a much more efficient use of photons and makes for a faster throughput device.
The Martin, et al. patent also describes (i) sensing particles by optical means, and (ii) act on the results of the sensing so as to (iii) manipulate the particles with laser light. Such optical sensing is fully compatible with the present invention.
Also involving both (i) fluidics and, separately, (ii) optical manipulation is U.S. Pat. No. 5,674,743 to Ulmer, assigned to SEQ, Ltd. (Princeton, N.J.), for METHODS AND APPARATUS FOR DNA SEQUENCING. The Ulmer patent concerns a method and apparatus for automated DNA s

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