Free-form fabrication using multi-photon excitation
First Claim
1. A multi-photon excitation system for activating a photoactivable precursor composition, the system comprising:
- a photon source generating a beam of photons, each photon having a wavelength approximately equal to an integer multiple of the wavelength necessary for single photon excitation in a photoactivatable precursor composition comprising at least two entities selected from the group consisting of proteins, peptides, nucleic acids, bioactive molecules and synthetic polymers;
wherein the at least two entities may be the same or different;
an optical system for directing the beam of photons to a focal point in at least one first location in the precursor composition;
a mechanism for causing relative motion in a prescribed coordinate system between the precursor composition and the photon beam; and
a controller for controlling the relative motion between the precursor composition and the photon beam.
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Abstract
A method wherein small, two- or three-dimensional structures are formed by multiple-photon-absorbed photopolymerization and/or cross-linking of a precursor composition. Use of multi-photon excitation allows fabrication of structures and structural features having at least one dimension of less than about one micron, preferably less than about 500 nm, more preferably less than about 250 nm, and most preferably of less than about 100 nm, in bulk phase as well as in solution, and from a wide variety of organic and inorganic precursor subunits, including synthetic polymers and biological polymers such as proteins, lipids, oligonucleotides, and the like. In one embodiment, use of two-photon far field optics allows the formation of structures having X-Y dimensions of less than about 300 nm and a Z dimension of less than about 500 nm, while use of three-photon far field optics allows the formation of structures having X-Y dimensions of less than about 250 nm and a Z dimension of less than about 300 nm. In a particularly preferred embodiment, use of a 4 pi optical configuration in combination with two-photon far field excitation allows the formation of structures having X-Y dimensions of less than about 150 nm and a Z dimension of less than about 100 nm. In another embodiment, use of multi-photon near field optics results in the formation of structures having X, Y, and Z dimensions of less than about 50 nm. In this embodiment, near field fabrication is achieved by two-photon excitation through fiber probes.
112 Citations
25 Claims
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1. A multi-photon excitation system for activating a photoactivable precursor composition, the system comprising:
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a photon source generating a beam of photons, each photon having a wavelength approximately equal to an integer multiple of the wavelength necessary for single photon excitation in a photoactivatable precursor composition comprising at least two entities selected from the group consisting of proteins, peptides, nucleic acids, bioactive molecules and synthetic polymers;
wherein the at least two entities may be the same or different;
an optical system for directing the beam of photons to a focal point in at least one first location in the precursor composition;
a mechanism for causing relative motion in a prescribed coordinate system between the precursor composition and the photon beam; and
a controller for controlling the relative motion between the precursor composition and the photon beam. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25)
a first laser generating the photon beam; and
a pump laser providing pump energy to the first laser.
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5. The multi-photon excitation system as set forth in claim 4 wherein the first laser comprises a Titanium sapphire laser.
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6. The multi-photon excitation system as set forth in claim 4 wherein the pump laser comprises a solid state laser or a gas laser.
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7. The multi-photon excitation system as set forth in claim 6 wherein the solid state laser comprises a diode pumped intracavity, frequency doubled Nd:
- host laser.
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8. The multi-photon excitation system as set forth in claim 7 Nd:
- host laser comprises a Nd;
YAG laser.
- host laser comprises a Nd;
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9. The multi-photon excitation system as set forth in claim 1 wherein the focusing optical system comprises a lens system.
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10. The multi-photon excitation system as set forth in claim 1 wherein the controller comprises a microprocessor.
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11. The multi-photon excitation system as set forth in claim 1 further comprising an interferometer for interfering a plurality of photon beams at the focal point in the least one first location in the precursor composition.
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12. The multi-photon excitation system as set forth in claim 11 wherein the interferometer comprises:
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a beam splitter for splitting the photon beam into a first beam and a second beam;
means for directing the first beam and the second beam to the precursor composition along separate pathways.
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13. The multi-photon excitation system as set forth in claim 12 further comprising a delay line for maintaining the lengths of the separate pathways within the coherence length of the photon source.
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14. The multi-photon excitation system as set forth in claim 12 wherein the focusing optical system comprises:
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a first lens system receptive of the first beam positioned on a first side of the precursor;
a second lens system receptive of the second beam positioned on a second side of the precursor opposite of the first side.
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15. The multi-photon excitation system as set forth in claim 12 wherein the focusing optical system focuses the first beam and the second beam to a mutual focal point.
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16. The multi-photon excitation system as set forth in claim 1 wherein the optical system comprises:
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a first lens system positioned at a first side of the precursor composition for focusing the beam of photons to a prescribed location in the precursor and collecting a fluorescence signal from the precursor composition;
a frequency selective device receptive of the fluorescence signal from the first lens system;
wherein the wavelength of the fluorescence signal is less than the wavelength of the beam of photons; and
a first detector receptive the fluorescence signal from the frequency selective device for converting the fluorescence signal to an electrical signal provided to the controller.
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17. The multi-photon excitation system as set forth in claim 16 wherein the frequency selective device comprises a dichroic mirror.
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18. The multi-photon excitation system as set forth in claim 16 wherein the optical system includes:
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a second lens system positioned at an opposing side of the precursor composition for collecting the fluorescence signal from the precursor composition; and
a second detector receptive the fluorescence signal from the second lens system for converting the fluorescence signal to an electrical signal provided to the controller.
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19. The multi-photon excitation system as set forth in claim 1 further comprising:
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a waveguide receptive of the photon beam for guiding the photon beam therealong; and
a probe receptive of the guided photon beam, the probe positioned in close proximity to the precursor composition.
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20. The multi-photon excitation system as set forth in claim 19 further comprising:
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an optical compensating device receptive of the photon beam for compensating for group velocity dispersion and self phase modulation; and
a set of waveguide couplers for coupling the photon beam into and out of the waveguide.
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21. The multi-photon excitation system as set forth in claim 20 wherein the compensating device comprises a grating pair.
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22. The multi-photon excitation system as set forth in claim 20 wherein the compensating device comprises a pair of prisms.
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23. The multi-photon excitation system as set forth in claim 19 wherein the waveguide comprises an optical fiber.
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24. The multi-photon excitation system as set forth in claim 19 wherein the probe comprises a pipette.
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25. The multi-photon excitation system as set forth in claim 1 wherein the optical system includes an interferometer having:
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a shutter controlled by the controller and receptive of the beam of photons for alternately passing and blocking the beam of photons;
a beam splitter receptive of the beam of photons for splitting the beam of photons into a first beam and a second beam;
a first lens system receptive of the first beam of photons and positioned at a first side of the precursor composition for focusing the first beam of photons to the precursor;
a delay line for introducing a delay between the first and second beam of photons;
a second lens system positioned at an opposite side of the precursor composition for focusing the second beam of photons to the precursor composition;
wherein the first and second beam of photons are precisely aligned spatially and temporally at the precursor.
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Specification