Method of using supercontinuum light for medical and biological applications

Abstract

A method and an apparatus are provided for producing SuperContinuum (SC) light for medical and biological applications is provided. Pulses are focused from a laser system into at least one of a pressurized cell and one or more fibers. A pump pulse is converted into the SC light at a specified rate of repetition. The SC light is applied at the specified rate of repetition to tissue for medical and biological applications.

Claims

1. A method of photo-activating molecular components within a matrix and/or cells of biological tissue to be treated for a specified medical condition, comprising the steps of exposing the tissue to pulses of supercontinuum (SC) light that has a spectral irradiance equal to at least 1 GW/nm cm.sup.2 that creates nonlinear optical effects in materials that excites molecules into upper electronic states and disassociates polyatomic bonds causing a breakdown in organic molecules for at least one of the following medical and biological applications: healing wounds, burns, cuts and bruises, fusing arteries, reducing scarring, producing angiogenesis, stimulating nerves, and killing bacteria, viruses and cancer cells; selecting at least one predetermined band of the supercontinuum light to excite electronic states of native molecules and/or overtone and combinational vibrational states of the native molecules associated with specified medical condition; and adjusting the rate of said pulses and duration of exposure to treat the specified medical condition using one, two and three photon absorption using selected zones in SC light.

2. A method as defined in claim 1, wherein said pulses are provided at about <100 femtoseconds (fs) to <10 ps.

3. A method as defined in claim 1, wherein said pulses are adjusted to have a repetition rate of approximately 1 kilohertz (kH) up to 100 Megahetz for different modelock operation of Ti sapphire laser.

4. A method as defined in claim 1, wherein the supercontinuum light is used to stimulate molecular activity of native molecules in the tissue by exciting electronic states and overtone and combination vibrational states of the native molecules via absorption using one and multi photon absorption.

5. A method as defined in claim 4, wherein a 280-500 nm band of the SC light is used to excite the electronic states of the native molecules, and an 800-2500 nm band is used to excite overtone and combination vibrational states of the native molecules.

6. A method as defined in claim 5, wherein the native molecules having excited electronic states comprise one or more of collagen, elastin, flavins, tryptophan, proteins, DNA, RNA and amino acids.

7. A method as defined in claim 5, wherein the native molecules having excited overtone and combination vibrational states comprise one or more of water, collagen and elastin.

8. A method as defined in claim 7, wherein absorption peaks of collagen are at one or more of 1750 nm, 1950 nm and 2250 nm, and absorption peaks for elastin are at one or more of 1600 nm, 1750 nm, 2150 nm, 2200 nm and 2300 nm.

9. A method as defined in claim 1, wherein the nonlinear optical effects comprise SHG, Stimulated Raman Scattering (SRS), 4 Wave Mixing (4WM), Third Harmonic Generation (THG) and self focusing.

10. A method as defined in claim 1, wherein a spectrum of the SC light covering UltraViolet (UV), visible and Near InfraRed (NIR) bands is created through at least one of Self Phase Modulation (SPM), Cross Phase Modulation (XPM) and 4WM use one, two or three photon absorption.

11. A method as defined in claim 1, wherein an 800-1700 nm band of the SC light stimulates nerves to be activated via vibrational excitation of water and lipid molecules near the nerves for therapeutic improvement of nerve based diseases.

12. A method of photo-activating molecular components within a matrix and/or cells of biological tissue to be fused or welded at a point where the tissue is cut, comprising the steps of exposing the tissue to pulses of supercontinuum (SC) light that has a spectral irradiance equal to at least 1 GW/nm cm.sup.2 that creates nonlinear optical effects in materials that excites molecules into upper electronic states and disassociates polyatomic bonds causing a breakdown in organic molecules for at least one of the following medical and biological applications: healing wounds, burns, cuts and bruises, fusing arteries, reducing scarring, producing angiogenesis, stimulating nerves, and killing bacteria, viruses and cancer cells; selecting a band of light spanning the supercontinuum from approximately 280 nm-2500 nm to induce water absorption by exciting electronic states and/or overtone and combinational vibrational states of the native molecules surrounding the cut tissue; and adjusting the rate of said pulses and duration of exposure to fuse a cut together with minimal scarring.

13. A method as defined in claim 12, wherein the band of light is centered at about 1445 nm.

14. A method as defined in claim 12, wherein said supercontinuum and UV light to visible regions are used to heal tissue wounds, bruises and burns.

15. A method as defined in claim 14, wherein the tissue is irradiated at a level of approximately 10 mW/cm.sup.2 of 100 mW/cm.sup.2.

16. A method as defined in claim 12, wherein the tissue is nerve used tissue and the supercontinuum light is used to stimulate neural activity.

17. A method as defined in claim 12, wherein the tissue is blood vessel tissue and the supercontinuum is used to heal and/or fuse the tissue and/or promote angiogenesis to enhance growth of blood vessels and flow of blood.

18. A method of photo-activating molecular components within a matrix and/or cells of biological substances comprising the steps of exposing the biological substances to pulses of supercontinuum (SC) light that has a spectral irradiance equal to at least 1 GW/nm cm.sup.2 that creates nonlinear optical effects in materials that excites molecules into upper electronic states and disassociates polyatomic bonds causing a breakdown in organic molecules for at least one of the following medical and biological applications: healing wounds, burns, cuts and bruises, fusing arteries, reducing scarring, producing angiogenesis, stimulating nerves, and killing bacteria, viruses and cancer cells; selecting at least one predetermined band of supercontinuum light to excite electronic states of native molecules and/or overtone and combinational vibrational states of the native molecules associated with the biological substances by multi-photon absorption; and adjusting the rate of said pulses and duration of exposure to rupture the bonds of the biological substances and ionize polyatomic molecules to neutralize the biological substances.

19. A method as defined in claim 1, wherein exposing comprises imaging one of brain, prostate, breast by linear and nonlinear (2 or 3 photon absorption) using the optical windows of tissue and water like media, in the wavelength windows or zones of less scattering to enhance imaging deep into tissue such as: 650 nm to 900 nm; 1150 nm to 1300 nm, 1600 nm to 1800 nm and 2100 to 2300 nm using an InGaAs and InSb CMOS or CCD cameras.

20. A method as defined in claim 1, wherein exposing comprises optical stimulation by using SC beams for applications on brain and nerve tissues for Alzheimer's, Parkinson, nerves in skin (shingles).

21. A method as defined in claim 1, wherein SC light is used for tissue welding of tissue wounds, bruises, and burns wherein welding strength follows the absorption spectrum of water from 1400 nm to 1600 nm and Collagen at 1600 nm to 1800 nm using an average irradiance of 100 mW/cm2.

22. A method as defined in claim 1, wherein SC pulsed lasers from 1850 nm to 2100 nm are used to stimulate nerves.

23. A method as defined in claim 1, wherein SC pulsed lasers are used to kill bacteria and viruses by exciting upper UV states with UV and blue light transitions.

24. A method as defined in claim 1, wherein SC light is used to provide SC IR laser pulse radiation at 1600 to 2300 nm for stimulation signal deep into the tissue up to mm allowing more selective excitation suitable for treating Parkinson Alzheimer, Shingles and other brain and nerve disorders from optical stimulation of nerves.

25. A method as defined in claim 1, wherein the SC light is used to stimulate neural activity using a portion of a signal spectra from 800 nm to 2300 nm to excite the vibrations of water and lipids in the tissue to transfer energy from water and lipids through overtone and combination vibrations to axons, neurons, and myelin complexes within the nerve and brain.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) The above and other aspects, features and advantages of the present invention will be more apparent from the following description when taken in conjunction with the accompanying drawings, in which:

(2) FIG. 1 is graph illustrating absorption spectral bands of electronic states of key molecules in cells and tissue structure, according to an embodiment of the present invention;

(3) FIGS. 2(a) AND 2(b) are graphs illustrating overtone and combination vibrational absorption bonds of water and collagen in tissue, according to an embodiment of the present invention;

(4) FIG. 3 is a diagram illustrating multiple photo transitions of polyatomic molecules to reach upper electronic states, according to an embodiment of the present invention; and

(5) FIG. 4 is a diagram illustrating an SC generation setup for medical and biological applications, according to an embodiment of the present invention.

DETAILED DESCRIPTION OF EMBODIMENTS OF THE PRESENT INVENTION

(6) Embodiments of the present invention are described in detail with reference to the accompanying drawings. The same or similar components may be designated by the same or similar reference numerals although they are illustrated in different drawings. Detailed descriptions of constructions or processes known in the art may be omitted to avoid obscuring the subject matter of the present invention.

(7) The terms and words used in the following description and claims are not limited to their dictionary meanings, but are merely used to enable a clear and consistent understanding of the invention. Accordingly, it should be apparent to those skilled in the art that the following description of embodiments of the present invention are provided for illustrative purposes only and not for the purpose of limiting the invention, as defined by the appended claims and their equivalents.

(8) It is to be understood that the singular forms a, an, and the include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to an identifier includes reference to one or more of such identifiers.

(9) The embodiments of the present invention relate to medical and biological applications using the SC. The SC light is incorporated into the field of medicine, specifically, for use in therapeutic biomedical applications in humans and animals, on the skin or within the body using optical fibers. Such applications may include the healing of wounds and bruises, the bonding of cut tissues, and the killing of bacteria and viruses through the generation of nonlinear effects. The SC light consists of ultrashort pulses spanning an ultrabroad spectral region at a high rate of repetition. The SC light spans the UV-visible-NIR spectrum with the ultrashort pulse duration being <10 ps, and typically <100 fs.

(10) The brightness of the SC light surpasses that of the sun hitting the surface of the earth, as well as other lasers over such a broad spectral coverage. The spectrum of the SC light is so wide that it can excite most molecules in tissue via single and multiple photon absorption from electronic transitions and combination and overtone vibrational transitions. The non-thermal excited state directly causes new interactions, chemical reactions, optical catalysts, enzyme actions and the formation of new bondings.

(11) The SC light stimulates molecular activity of the native molecules in the tissue by exciting their electronic states and overtone and combination vibrational states via absorption. It is well known that excited energy states of molecules are the most active. For example, the energy state of oxygen, which is normally in triplet state .sup.3O.sub.2, can be excited to a singlet state .sup.1O.sub.2 in order to oxidize surrounding molecules. The key molecules and bonds in tissue that can be excited by the SC light include collagen, elastin, tryptophan, water, proteins, NAPHs, genes, porphyrins, peptides, flavins, amino acids, blood, hemoglobin, and amide I, II, III, A.

(12) On a molecular level, the distribution of excited molecules among higher energy states will appear to be hot at temperature T.sub.0, since the higher energy states are far beyond the normal populations. The photoexcited molecules behave as if the system was heated to an extreme temperature (T.sub.0) during the pumping time of <10 ps. However, the host containing the non-excited molecules will actually be at room temperature T.sub.RT. The chemical reactions will proceed at a much faster rate at the hot temperature, T.sub.0, overcoming any potential barriers in reaction coordinate space and acting like an optical catalyst. There is no damage to the host since the tissue is not actually hot.

(13) For example, photoexcited hot (T.sub.0) molecules of water and collagen will cause rebonding of the hydrogen bonds and collagen-collagen-H.sub.2O-bonds, where the collagen rewinds via H.sub.2O coupling and matches up the ends of chains. Additionally, new collagen will form by photo stimulation.

(14) The entire ultra-broad spectrum of the SC, or a selected portion using optical filters, can be used to selectively excite a particular molecular group or bonds. In tissue, there are many key native molecules with absorptions from electronic transitions S.sub.0.fwdarw.S.sub.1, S.sub.2 covering a 280-500 nm band. The absorption spectral bands of electronic states of key molecules in cells and tissue structure are shown in FIG. 1. These molecules include, for example, collagen at 340 nm, elastin at 380 nm, flavins at 300 nm, tryptophan at 280 nm, proteins at 280-400 nm, DNA at 230-280 nm, and RNA at 240-280 nm.

(15) There are also key native molecules with absorptions from overtone and combination vibrational modes covering the NIR band from 800-2500 nm. These molecules include water at 900-1600 and 1900 nm, collagen at 1600-2500 nm, and elastin at 1700-2400 nm. The overtone and combination vibrational absorption bonds of water and collagen in tissue are shown in FIG. 2. The absorption peaks of collagen are, for example, at 1750 nm, 1950 nm, 2250, while those for elastin are, for example, at 1600 mu, 1750 nm, 2150 nm, 2200 nm, and 2300 nm.

(16) FIG. 3 shows multiple photon transitions of polyatomic molecules to reach upper electronic states for the ionization and destruction of bacteria, viruses, and cancers. The SC light can have a spectral irradiance of GW/nm cm.sup.2 from a selected spectral portion to create nonlinear optical effects in materials to enter into an extreme UV region and excite molecules in upper electronic states, S.sub.n (n=2, 3, 4, . . . ). This disassociates polyatomic bonds and causes an avalanche breakdown in organic molecules to kill bacteria, viruses, and cancers as shown in Equation (1) below:

(17) ##STR00001##

(18) The ground state S.sub.0 absorbs photons from photon energy by of SC followed by ionization and disassociation generating avalanche electrons e to break bonds as shown in FIG. 3.

(19) FIG. 4 is a diagram illustrating an example of a setup for medical and biological applications for using the SC light from a fiber or gas cell, according to an embodiment of the present invention. In accordance with an embodiment of the present invention, <100 fs pulses from a laser system 402 are focused into a pressurized cell 404 containing a rare gas, or a fiber 406, to convert an entire pump pulse of 1 mJ into the SC light at a repetition rate of 1 kiloHertz (kHz). The laser system may be a Ti-sapphire and Second Harmonic Generation (SHG) laser system with 400 nm and 800 nm pulses. The laser system may also be a Cr:Forsterite laser system with 1250 mm pulses. The laser system may further be a LiInGeO4 (LIGO) or LiInSiO4 (LISO) laser system with 1500 nm pulses. The pressurized cell 404 has a length ranging from 100-150 cm, and preferably 100 cm. The pressurized cell 404 contains 2-10 atoms of a rare gas, such as (Ar), (Kr) or (Xe).

(20) The pulses are focused through a long focus lens 408, having a focal length between approximately 100-200 cm, and preferably 150 cm, for introduction into pressurized cell 404. Alternatively, the pulses may be focused through a microscope objective lens at approximately 10-40 magnification for introduction to the fiber 406. The pulses proceed through an exiting lens to an optical filter wheel 410 with narrow band filters that are approximately 5-100 nm in width. A resulting center frequency, which covers UV, visible and NIR regions, is then delivered to wound for healing effects.

(21) For an SC span of about 1000 nm, a peak spectral energy is defined as shown in Equation (2) below:

(22) $\begin{array}{cc}\frac{1mJ}{1000\mathrm{nm}}& \left(2\right)\end{array}$

(23) This value will give the peak spectral energy as defined as shown in Equation (3) below:

(24) $\begin{array}{cc}{\mathrm{.Math.}}_{}=\frac{1\mathrm{.Math.J}}{\mathrm{nm}}.& \left(3\right)\end{array}$

(25) A peak spectral energy flux (irradiance-energy per area) of the SC light for a beam size of 1 nm is defined as shown in Equation (4) below:

(26) $\begin{array}{cc}\frac{{\mathrm{.Math.}}_{}}{A}=\frac{100\mathrm{.Math.}J}{\mathrm{nm}{\mathrm{cm}}^2}& \left(4\right)\end{array}$

(27) For a 100 fs pulse, a peak spectral power intensity is defined as shown in Equation (5) below:

(28) $\begin{array}{cc}\frac{P_{}}{A}=\frac{{10}^9\mathrm{watt}}{\mathrm{nm}{\mathrm{cm}}^2}=\frac{\mathrm{GW}}{\mathrm{nm}{\mathrm{cm}}^2}.& \left(5\right)\end{array}$

(29) This peak spectral power flux is sufficient to produce a variety of nonlinear optical effects via .sub.2 and .sub.3 processes such as SHG, Stimulated Raman Scattering (SRS), 4WM, Third Harmonic Generation (THG) and self-focusing at different spectral wavelength bands of 1 nm to 10 nm at 1 GW/cm.sup.2 to 10 GW/cm.sup.2.

(30) Focusing this SC beam into 100 m spot size results in a peak spectral power flux at the focal spot as defined in Equation (6) below:

(31) $\begin{array}{cc}\frac{P_{}}{A}=\frac{{10}^{11}\mathrm{watt}}{\mathrm{nm}}=0.1\frac{\mathrm{Terawatt}}{\mathrm{nm}}& \left(6\right)\end{array}$

(32) There is enough power to ionize most materials and create nonlinear optical effects with a spectral selected window of a few nanometers. This power level of the SC light in blue can produce two, three and higher photon absorption transitions in tissue, bacteria and viruses, such that these elements and even cancers may be destroyed.

(33) From Equation (4) above, the average spectral brightness (average spectral irradiance

(34) $\left(\frac{\mathrm{power}}{\mathrm{area}}\right))$
of SC for a 1 kHz rate pulse train is defined as shown in Equation (7) below:

(35) $\begin{array}{cc}\frac{{\stackrel{\_}{P}}_{}}{A}=\frac{100j}{{\mathrm{cm}}^2\mathrm{nm}}\left({10}^3\mathrm{Hz}\right)=100\frac{\mathrm{milliwatts}}{\mathrm{nm}{\mathrm{cm}}^2}& \left(7\right)\end{array}$

(36) The brightness of the SC light over the entire bandwidth of 1000 nm is defined as shown in Equation (8) below:

(37) $\begin{array}{cc}\frac{\stackrel{\_}{P}}{A}=\frac{100\mathrm{watts}}{{\mathrm{cm}}^2}& \left(8\right)\end{array}$

(38) The brightness of the sun hitting the surface of the earth at 1370 watt/m.sup.2 is defined as shown in Equation (9) below:

(39) $\begin{array}{cc}\frac{\stackrel{\_}{P}}{A}=0.137\frac{\mathrm{watt}}{{\mathrm{cm}}^2}& \left(9\right)\end{array}$

(40) The solid angle of the sun is 710.sup.5 radii and SC is 410.sup.6 radii. The full. SC white light brightness is more than the sun hitting the earth. Typical irradiance needed for healing is 10 mW/cm.sup.2-100 mW/cm.sup.2 in visible and NIR using selected wavelengths. The SC light has this irradiance.

(41) The brightness of the sun or an intensity of a 1000 Watt/m.sup.2 DC lamp has 0.1 W/cm.sup.2, which gives an energy within 10.sup.13 sec over an area of 1 cm.sup.2, is defined in Equation (10) below:
E=10.sup.14J(10)

(42) The energy of SC over 1 cm.sup.2 in a one nanometer band is 100 J, i.e. 10.sup.4 J. The ratio of energies between SC and E is defined in Equation (11) below:
E.sub.SC/E=10.sup.4/10.sup.14=10.sup.10(11)

(43) The energy of SC is much larger than Continuous Wave (CW) by over 10.sup.10 for 100 fs.

(44) The number of photons in SC at the wavelength of 500 nm is defined in Equation (12) below.
N.sub.SC500=2.510.sup.14 photons,(12)

(45) The number of photons in the light of the sun within 10.sup.13 sec time span is defined in Equation (13) below:
N.sub.sun=2.510.sup.4 photons(13)

(46) The ratio of Equation (14) can induce nonthermal reactions and changes in materials to heal.
N.sub.SC500/N.sub.sun=10.sup.10,(14)

(47) Referring again to FIG. 4, a microstructure or photonic crystal fiber 406 can be utilized in place of the pressurized cell 404. Small core microstructure fibers with an air filling factor (f) can cover UV, visible, and NIR regions using Self Phase Modulation (SPM), Cross Phase Modulation (XPM), 4WM, and soliton at pump wavelengths near zero dispersion fibers in the visible and NIR regions. For example, a 1 m core quartz fiber has two zero group velocity dispersion points at both 550 nm and 1200 nm wavelengths for f=1, and a 1.7 m core fiber has two zero dispersion points at 750 nm and 1500 nm with a full factor of f=0.5. These fibers will produce the SC light from blue to NIR.

(48) About a 600 nm diameter core fiber has two zero dispersion wavelengths at 350 nm and 1200 nm. This fiber is ideal for SC generation and covers the spectral band from 300 nm to 1400 nm spanning UV to NIR. The 1 m core fiber covers the SC light spectrum from 400 to 1400 nm using both SPM and XPM.

(49) Thus, as shown in FIG. 4, the SC light can be used for therapeutic applications of healing wounds, healing bruises, healing burns, fusing cut tissue, and welding tissues by exciting electronic and vibrational states of the underlying molecules in tissue and skin. Tissues may be healed with less scarring, and arteries may be healed and fused with reduced scarring. The SC light can produce angiogenesis for an increase in new blood vessels, blood flow and improved healing. A small room may also be flooded with the SC light to heal tissue damage and wounds of patients.

(50) As described above, upper electronic state excitation by multi photon absorption (2, 3, and 4 photons from the SC) can lead to the rupturing of bonds and ionization of polyatomic molecules, such as bacteria, viruses, and cancers.

(51) Nerve stimulation using electric pulses is used for therapeutic treatment of Parkinson, Alzheimer, and other brain and nerve diseases. Electrical stimulation of nerves requires contacts with metal electrodes inserted into tissue to make contact precisely near nerves in skin. Optical stimulation can deliver the signal deep into the tissue allowing more selective excitation. IR laser pulse radiation at 1600 to 2300 nm is suitable to stimulate nerves. The SC light offers greater potential to stimulate neural activity using a portion of a signal spectra from 800 nm to 1700 nm to excite the vibrations of water and lipids in the tissue to transfer energy from water and lipids through overtone and combination vibrations to axons and myelin complexes within the nerve.

(52) Additional uses for the SC light in medical and biological applications include its use as a lamp in a projector during surgery to differentiate anatomical structures in selected colors. Specifically, deoxygenation and oxygenation regions and cancerous and non-cancerous regions may be differentiated, via scattering and emission from the key molecules in tissues described above.

(53) While the invention has been shown and described with reference to certain embodiments thereof, it will be understood by those skilled in the art that various changes in form and detail may be made therein without departing from the spirit and scope of the invention as defined by the appended claims and their equivalents.