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WO2004025284A1 - Procede et systeme laser pour claquage optique ameliore - Google Patents

Procede et systeme laser pour claquage optique ameliore Download PDF

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Publication number
WO2004025284A1
WO2004025284A1 PCT/US2003/027146 US0327146W WO2004025284A1 WO 2004025284 A1 WO2004025284 A1 WO 2004025284A1 US 0327146 W US0327146 W US 0327146W WO 2004025284 A1 WO2004025284 A1 WO 2004025284A1
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WO
WIPO (PCT)
Prior art keywords
composition
additive
nanodevice
nanocomposite
dendrimer
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2003/027146
Other languages
English (en)
Inventor
Jing Yong Ye
Theodore B. Norris
James R. Baker
Lajos P. Balogh
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
University of Michigan System
University of Michigan Ann Arbor
Original Assignee
University of Michigan System
University of Michigan Ann Arbor
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from US10/637,343 external-priority patent/US7474919B2/en
Application filed by University of Michigan System, University of Michigan Ann Arbor filed Critical University of Michigan System
Priority to AU2003260133A priority Critical patent/AU2003260133A1/en
Publication of WO2004025284A1 publication Critical patent/WO2004025284A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y15/00—Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0093—Detecting, measuring or recording by applying one single type of energy and measuring its conversion into another type of energy
    • A61B5/0095—Detecting, measuring or recording by applying one single type of energy and measuring its conversion into another type of energy by applying light and detecting acoustic waves, i.e. photoacoustic measurements
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B8/00—Diagnosis using ultrasonic, sonic or infrasonic waves
    • A61B8/48—Diagnostic techniques
    • A61B8/481—Diagnostic techniques involving the use of contrast agents, e.g. microbubbles introduced into the bloodstream
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/1702—Systems in which incident light is modified in accordance with the properties of the material investigated with opto-acoustic detection, e.g. for gases or analysing solids
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/71—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light thermally excited
    • G01N21/718—Laser microanalysis, i.e. with formation of sample plasma
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N29/00—Investigating or analysing materials by the use of ultrasonic, sonic or infrasonic waves; Visualisation of the interior of objects by transmitting ultrasonic or sonic waves through the object
    • G01N29/22—Details, e.g. general constructional or apparatus details
    • G01N29/24—Probes
    • G01N29/2418—Probes using optoacoustic interaction with the material, e.g. laser radiation, photoacoustics
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2291/00—Indexing codes associated with group G01N29/00
    • G01N2291/02—Indexing codes associated with the analysed material
    • G01N2291/024—Mixtures
    • G01N2291/02433—Gases in liquids, e.g. bubbles, foams
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2291/00—Indexing codes associated with group G01N29/00
    • G01N2291/02—Indexing codes associated with the analysed material
    • G01N2291/024—Mixtures
    • G01N2291/02475—Tissue characterisation
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2291/00—Indexing codes associated with group G01N29/00
    • G01N2291/02—Indexing codes associated with the analysed material
    • G01N2291/024—Mixtures
    • G01N2291/02491—Materials with nonlinear acoustic properties

Definitions

  • This invention relates to laser-based methods and systems for enhancing optical breakdown.
  • U.S. Patent No. 6,146,375 discloses a device for internal surface sclerostomy and U.S. Patent No. 6,391,020 discloses a system for destroying material using optical radiation and ultrasound waves.
  • U.S. Patent No. RE 37,585 discloses a method to localize laser-induced breakdown.
  • the breakdown threshold is also determined by the nature of the material itself. So far, much less attention has been paid to altering the breakdown threshold and achieving a controllable breakdown by modifying the material, although LIOB in well-designed materials has a wide range of potential applications.
  • Dendrimers are a class of macromolecules possessing a highly- branched three-dimensional architecture and well-controlled size, shape and functionality.
  • U.S. Patent No. 6,471,968 discloses a multifunctional nanodevice platform in the form of dendrimer complex.
  • An object of the present invention is to provide an improved laser- based method and system for enhancing optical breakdown by altering the LIOB threshold of a composition or material by incorporating an additive such as metal nanoparticles into the composition which significantly enhances the electric field localized at their immediate surroundings.
  • a laser-based method for enhancing optical breakdown includes providing a composition having an additive incorporated therein.
  • the composition has a desired photodisruption threshold substantially lower than a photodisruption threshold of the composition without the additive.
  • the method also includes generating at least one laser pulse having a predetermined pulse characteristic based on the desired photodisruption threshold.
  • the method further includes propagating the at least one laser pulse through the composition to a photodisruption region determined by the location of the additive in the composition.
  • the additive decreases the photodisruption threshold associated with the at least one laser pulse in the vicinity of the additive.
  • the composition may include at least one nanodevice having the additive and a linked agent targeted to a specific biological structure or tissue.
  • the at least one nanodevice may include a dendrimer-based nanodevice.
  • the additive may include metal nano particles or domains.
  • the composition may include polymer macromolecules which are a host for the additive.
  • the polymer macromolecules may form at least one dendrimer-based nanodevice.
  • the composition may further include at least one metal nanocomposite.
  • the at least one laser pulse may include an ultrashort laser pulse.
  • the composition may further include at least one nanocomposite having the additive, and the at least one laser pulse may cause a disruption change to the at least one nanocomposite.
  • the composition may still further include at least one nanodevice having the additive and a linked therapeutic agent, and the at least one laser pulse may cause the at least one nanodevice to release the linked therapeutic agent.
  • the composition may still further include at least one nanodevice having the additive, and the at least one laser pulse may cause a disruption change to the at least one nanodevice with little or no damage to material adjacent to the nanodevice.
  • the at least one laser pulse may cause a disruption change to the at least one nanocomposite with little or no change to material adjacent to the at least one nanocomposite.
  • the at least one laser pulse may cause a disruption change to the nanocomposite which, in turn, causes a disruption change to material adjacent to the nanocomposite .
  • the desired photodisruption threshold may be several or more times less than the photodisruption threshold of the composition without the additive.
  • the desired photodisruption threshold may be one or more orders of magnitude less than the photodisruption threshold of the composition without the additive.
  • composition without the additive may include a substantially pure dendrimer and the composition with the additive may include at least one nanocomposite.
  • the composition may include a plurality of individual nanodevices, and the at least one laser pulse may aggregate the individual nanodevices.
  • the composition may further include a plurality of nanodevices.
  • Each of the nanodevices may be a nanocomposite having the additive.
  • Each nanocomposite may be a dendrimer nanocomposite.
  • Each of the dendrimer nanocomposites may be a metal/dendrimer nanocomposite.
  • the at least one pulse may cause a change to material in a vicinity of the composition, or may cause material in the vicinity of the composition to be heated, or may cause material in the vicinity of the composition to be broken down.
  • the composition may include at least one optical data storage nanodevice.
  • the at least one optical data storage nanodevice may include a dendrimer-based nanodevice.
  • the at least one nanodevice may include a dendrimer-based nanodevice.
  • a system for enhancing optical breakdown utilizing a composition having an additive incorporated therein.
  • the composition has a desired photodisruption threshold substantially lower than a photodisruption threshold of the composition without the additive.
  • the system includes a pulsed laser for generating at least one laser pulse having a predetermined pulse characteristic based on the desired photodisruption threshold.
  • An optical subsystem directs the at least one laser pulse to the composition.
  • the at least one laser pulse propagates through the composition to a photodisruption region determined by the location of the additive in the composition.
  • the additive decreases the photodisruption threshold associated with the at least one laser pulse in the vicinity of the additive.
  • FIGURE la is a schematic view illustrating the architecture of a dendrimer
  • FIGURE lb is a schematic view illustrating the architecture of a dendrimer nanocomposite (DNC) used in the method and system of the present invention
  • FIGURE 2a is a graph which illustrates the change of THG signal during LIOB of DNCs for eight events under laser irradiation of 9 mWs;
  • FIGURE 2b is a graph which illustrates the THG signal from the pure PAMAM-quartz under irradiation of 90 mW; there is no LIOB observed;
  • FIGURE 3 is a schematic view illustrating the targeting of cancer cells using a dendrimer-based, smart therapeutic nanodevice
  • FIGURE 4a is a graph which illustrates TPF power as functions of the concentrations of G5-FI and G5-FI-FA.
  • FIGURE 4b is a graph of a dose-response curve for the binding of
  • G5-FI and G5-FI-FA on KB cells the G5-FI-FA specific binding is obtained by subtracting the non-specific G5-FI signal; at saturation, the level of G5-FI-FA bound was about 2 pmol/10 6 cells.
  • the present invention involves an improved laser-based method and system for enhancing optical breakdown using an additive such as metal nanoparticles or metal nanodomains which remarkably change the laser-induced optical breakdown (LIOB) threshold of a material, owing to a large enhancement of the local electric field.
  • LIOB is implemented using femtosecond laser pulses in a gold/dendrimer hybrid nanocomposite (DNC).
  • DNC gold/dendrimer hybrid nanocomposite
  • Third- harmonic generation measurements have been employed as a sensitive way for monitoring the LIOB in situ and in real-time. The observed statistical behavior of the breakdown process is attributed to a laser-driven aggregation of individual DNC particles.
  • the breakdown threshold value of the DNC has been found to be up to two orders of magnitude lower than that of pure dendrimers or normal tissues.
  • Dendrimer-based nanoparticles conjugated to linker molecules can be used to selectively deliver the nanoparticles to targeted components in biological systems, and the use of metal nanoparticles or metallic nanocomposites can significantly reduce laser-induced breakdown thresholds, which enhances the effect of triggering release of therapeutics from a drug delivery system with femtosecond laser pulses.
  • a model system, a gold/dendrimer nanocomposite (DNC), is described using femtosecond laser pulses.
  • a generation-5 poly(amidoamine) (PAMAM) with ethylenediamine (EDA) core was used as a template to form a hybrid nanocomposite.
  • the laser system used was based on a 250 kHz regeneratively amplified Ti: sapphire laser.
  • the amplified pulses, with pulse duration of 100 fs and wavelength of 793 nm, were attenuated with a variable neutral density filter, and focused at the front interface between the quartz cuvette and the DNC solution using an /: 1 off-axis (60°) parabola.
  • Third-harmonic generation (THG) was utilized as a sensitive method for monitoring LIOB in the sample.
  • the THG from the interface was spatially separated from the fundamental transmitted light using a Brewster quartz prism and further filtered with two UV interference band pass filters with center wavelength of 265 nm.
  • the THG signal was monitored during the LIOB process with a photon counting system.
  • Figures la and lb show the architecture of dendrimer and DNC, respectively, and Figure lc shows the laser spectrum and the absorption spectra of pure PAMAM and DNC methanol solutions.
  • the DNC has an absorption maximum around 272 nm, which results from the plasmon resonance of the incorporated gold nanodomains. This absorption peak is close to the one-third of the laser wavelength, while there is no absorption in the wavelength regime of fundamental light.
  • THG time to go through the material properties.
  • the variation of THG signal sensitively reflects the change of the material properties, because the intensity of THG is related to the difference of the refractive index or third-order nonlinear susceptibility of the materials on both sides of a laser focus spot at an interface.
  • THG was previously employed to probe the microscopic structure of transparent samples. The THG measurement was used to monitor the LIOB in the DNC sample. In contrast to conventional criteria for determining breakdown threshold by visual acquisition and ablation depth measurement, which is not well defined for the former and not in real-time for the latter, the THG measurements provided a sensitive way to monitor the LIOB in situ and in real-time.
  • Figure 2a shows eight events of breakdown of the DNC sample under irradiation power of 9 mW, where after each breakdown event, the sample was shifted to a new position.
  • the rise of the THG signal occurs when a shutter in the laser beam is opened, while the sudden drop of THG indicates the breakdown.
  • Figure 2b shows that the THG signal from the interface of the quartz and the pure template PAMAM dendrimer remains unchanged even under much higher irradiation power.
  • a breakdown threshold of the DNC was obtained as low as 0.9 mW (9.5 mJ/cm 2 ), while the breakdown threshold of a pure PAMAM dendrimer (without gold) was found to be 102 mW (1080 mJJ/cm 2 ), which is 113- fold higher than that of the DNC sample.
  • the breakdown threshold of the DNC is also two orders of magnitude lower than the typical breakdown threshold of a tissue.
  • dendrimers When dendrimers are used as a host for metal nanodomains as described herein, one can achieve selectively targeting biological systems, such as a tumor, by modifying the dendrimer peripheral branches with a target agent, as shown in Figure 3.
  • the large number of peripheral branches of a dendrimer allows one to attach various functional groups to a single dendrimer or to a tecto-dendrimer containing a core dendrimer surrounded by other functional dendrimers. This is one of the remarkable advantages of using dendrimer nanoparticle composites over a pure metal nanoparticle.
  • targets to direct the dendrimer-based nanodevice There are two possible types of targets to direct the dendrimer-based nanodevice. The first involves the use of cell receptors that are present in normal cells, but over-expressed in cancer cells. These targets would include the receptors for growth factors and would be useful in that they would increase the uptake of the nanodevice specifically in cancer cells and internalize the device through receptor- mediated pinocytosis.
  • An alternative approach would be to target through tumor- specific antigens. This involves targeting cancer-specific proteins such as Her2. In either case, antibodies or specific ligands for the various receptors coupled to dendrimers will be used for targeting.
  • the specific targeting capability of a conjugated dendrimer has been demonstrated in an uptake experiment of a targeted drug delivery agent into cancer cells.
  • the dendrimers used are conjugated both to a fluorescent dye to enable optical sensing of the presence of dendrimers in the cells, and to folic acid (FA), which enables the dendrimers to be selectively taken up by FA-receptor-positive KB cells (a sub-line derived from the cervical carcinoma HeLa cell line).
  • FA folic acid
  • the binding of G5-FI-FA [generation-5 poly (amidoamine) (PAMAM) dendrimers (G5) conjugated with fluorescein isothiocyanate (FI) and FA has been investigated as well as control G5-FI dendrimer to KB cells.
  • the plasmon resonance of the DNC used is in the UV region, far away from the laser wavelength. This suggests that aggregation of the DNCs may be necessary in order to form a cluster with a plasmon resonance near the laser frequency.
  • the existence of the waiting time before breakdown implies that it takes some time for individual DNCs to form aggregates and for the aggregates to grow to a critical size.
  • the aggregation leads to a shift of the plasmon resonance in a local region toward the laser wavelength, thus the field of light is enhanced and eventually to exceed the breakdown threshold.
  • the fluctuation of the waiting time reflects the statistical behavior of the aggregation process. Moreover, it has been observed that the waiting time becomes notably shorter when the irradiation power is higher than 40 mW, which is still at a power level lower than the breakdown threshold of a pure dendrimer by a factor of 2.5. The sudden decrease of the waiting time implies that there is a change of the breakdown mechanism for the power above 40 mW.
  • DNC unique nature opens up a wide range of potential applications.
  • the extremely low breakdown threshold would allow one to selectively break down and target DNC molecules to trigger release of encapsulated therapeutics, while avoiding unwanted damage to surrounding tissues.
  • the other potential application is to use DNC to directly break down an organism within a cell (such as a cancer cell) through a nanoheating effect, because the highly enhanced local field of light due to the incorporated metal nanoparticles when irradiated with femtosecond laser pulses is well confined within nanometer region around the DNC.
  • DNCs may also be used as high- density optical data storage materials owing to their nanometer size and high photosensitivity.

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Abstract

Cette invention se rapporte à un additif, se présentant de préférence sous la forme de nanoparticules ou de nanodomaines métalliques, qui améliore considérablement un procédé et un système laser conçus pour induire un claquage optique. L'utilisation d'impulsions laser ultracourtes pour induire un claquage induit par éclair laser (LIB) dans des nanoparticules ou des nanocomposites métalliques permet de réduire considérablement le seuil d'énergie laser requise pour le claquage induit par éclair laser. Ces particules métalliques nanométriques (de l'ordre du sous-micron) permettent de commander le processus de claquage induit par éclair laser. Ces nanoparticules peuvent être synthétisées, afin de cibler des structures ou des tissus biologiques spécifiques (les nanoparticules de dendrimère constituent un système pour lequel ce ciblage a pu être mis en évidence). Cette invention offre ainsi la possibilité d'effectuer un claquage induit par éclair laser pour le traitement ou la microchirurgie ciblés du cancer.
PCT/US2003/027146 2002-08-29 2003-08-27 Procede et systeme laser pour claquage optique ameliore Ceased WO2004025284A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2003260133A AU2003260133A1 (en) 2002-08-29 2003-08-27 Laser-based method and system for enhanced optical breakdown

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US40686102P 2002-08-29 2002-08-29
US60/407,018 2002-08-29
US60/406,861 2002-08-29
US10/637,343 2003-08-08
US10/637,343 US7474919B2 (en) 2002-08-29 2003-08-08 Laser-based method and system for enhancing optical breakdown

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11344358B2 (en) 2018-06-22 2022-05-31 Avava, Inc. Apparatus for selective treatment of tissue

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001087348A2 (fr) * 2000-05-12 2001-11-22 The Regents Of The University Of Michigan Plate-forme multifonction du type nanodispositif

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001087348A2 (fr) * 2000-05-12 2001-11-22 The Regents Of The University Of Michigan Plate-forme multifonction du type nanodispositif

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
JING YONG YE ET AL: "Enhancement of laser-induced optical breakdown using metal/dendrimer nanocomposites", APPLIED PHYSICS LETTERS, 11 MARCH 2002, AIP, USA, vol. 80, no. 10, pages 1713 - 1715, XP002266553, ISSN: 0003-6951 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11344358B2 (en) 2018-06-22 2022-05-31 Avava, Inc. Apparatus for selective treatment of tissue

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