U.S. patent application number 14/629617 was filed with the patent office on 2015-09-17 for production of organic compound nanoparticles with high repetition rate ultrafast pulsed laser ablation in liquids.
The applicant listed for this patent is IMRA America, Inc.. Invention is credited to Yong CHE, Zhendong HU.
Application Number | 20150258631 14/629617 |
Document ID | / |
Family ID | 44354201 |
Filed Date | 2015-09-17 |
United States Patent
Application |
20150258631 |
Kind Code |
A1 |
HU; Zhendong ; et
al. |
September 17, 2015 |
Production Of Organic Compound Nanoparticles With High Repetition
Rate Ultrafast Pulsed Laser Ablation In Liquids
Abstract
Disclosed is a method of producing a chemically pure and stably
dispersed organic nanoparticle colloidal suspension using an
ultrafast pulsed laser ablation process. The method comprises
irradiating a target of an organic compound material in contact
with a poor solvent with ultrashort laser pulses at a high
repetition rate and collecting the nanoparticles of the organic
compound produced. The method may be implemented with a high
repetition rate ultrafast pulsed laser source, an optical system
for focusing and moving the pulsed laser beam, an organic compound
target in contact with a poor solvent, and a solvent circulating
system to cool the laser focal volume and collect the produced
nanoparticle products. By controlling various laser parameters, and
with optional poor solvent flow movement, the method provides
stable colloids of dispersed organic nanoparticles in the poor
solvent in the absence of any stabilizing agents.
Inventors: |
HU; Zhendong; (Ann Arbor,
MI) ; CHE; Yong; (Ann Arbor, MI) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
IMRA America, Inc. |
Ann Arbor |
MI |
US |
|
|
Family ID: |
44354201 |
Appl. No.: |
14/629617 |
Filed: |
February 24, 2015 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
12951496 |
Nov 22, 2010 |
8992815 |
|
|
14629617 |
|
|
|
|
61302984 |
Feb 10, 2010 |
|
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Current U.S.
Class: |
424/489 ;
264/400; 514/679 |
Current CPC
Class: |
B23K 26/144 20151001;
A61K 9/10 20130101; A61K 31/12 20130101; B82Y 40/00 20130101; Y10S
977/889 20130101; B01J 13/0086 20130101; A61K 9/14 20130101; Y10S
977/901 20130101; B23K 26/146 20151001; B23K 26/0624 20151001 |
International
Class: |
B23K 26/06 20060101
B23K026/06; A61K 9/10 20060101 A61K009/10; A61K 9/14 20060101
A61K009/14; B23K 26/14 20060101 B23K026/14; A61K 31/12 20060101
A61K031/12 |
Claims
1. A method of producing nanoparticle colloidal suspensions of
organic materials in poor solvents, comprising the steps of: a)
irradiating a shaped bulk target of an organic compound material
with an ultrashort pulsed laser beam having a pulse duration of 500
picoseconds or less, at least a portion of the shaped bulk target
in contact with a liquid, the liquid being substantially
transparent at a wavelength of the pulsed laser beam, the
irradiation generating a stable nanoparticle suspension of the
organic compound material in the liquid by ablation; and b)
producing one or both of relative movement of the liquid relative
to a surface of the target and relative motion between the pulsed
laser beam and the target.
2. The method of claim 1, wherein step a) comprises irradiating
with a pulsed laser beam having a repetition rate in the range of
about 1 Hz to 100 MHz.
3. The method of claim 2, wherein step a) comprises irradiating
with a pulsed laser beam having a pulse duration ranging from 10
femtosecond to 500 picosecond.
4. The method of claim 1, wherein step a) comprises irradiating
with a pulsed laser beam having a pulse energy ranging from 1
nano-Joule to 10 mili-Joule.
5. The method of claim 1, wherein step a) comprises irradiating
with a pulsed laser beam having a laser fluence on the target
surface of from 10 milli-Joules/cm.sup.2 to 5 Joules/cm.sup.2.
6. The method of claim 1, further comprising providing deionized
water having a resistance of 0.05 M Ohmcm or greater as the
liquid.
7. The method of claim 1, wherein step b) comprises flowing the
liquid across a surface of the target at a rate of 1 milliliter per
second or greater.
8. The method of claim 1, further comprising providing a vibrating
mirror having a frequency of 10 Hz or greater and an angular
amplitude of 0.1 mrad or greater, said vibrating mirror moving said
laser beam over said target.
9. The method of claim 8, comprising guiding the laser beam
movement on the target such that a focal spot of the laser beam
moves at a speed of 0.1 meters per second or greater over the
target.
10. A nanoparticle colloidal suspension prepared according to the
method of claim 1.
11. A colloidal suspension of nanoparticles in a liquid comprising
nanoparticles having an average diameter of 100 nanometers or less,
wherein said colloidal suspension is stable at 25.degree. C. for at
least 7 days in the absence of any stabilizing agents or surface
active agents with no aggregation of said nanoparticles.
12. The colloidal suspension as recited in claim 11 wherein said
colloidal suspension is stable at 25.degree. C. for at least 2
months.
13. The colloidal suspension as recited in claim 11 wherein said
colloidal suspension consists essentially of said nanoparticles and
said liquid.
14. The colloidal suspension as recited in claim 11 wherein said
liquid is deionized water have a resistivity of greater than 0.05
MOhmcm.
15. The colloidal suspension as recited in claim 11 wherein said
liquid is deionized water having a resistivity of greater than 1
mOhmcm.
16. The colloidal suspension as recited in claim 11 wherein said
nanoparticles have a charge.
17. The colloidal suspension as recited in claim 11 wherein said
nanoparticles comprise curcumin.
18. The colloidal suspension as recited in claim 11 wherein said
nanoparticles are poorly soluble in said liquid.
19. The colloidal suspension as recited in claim 11 wherein said
nanoparticles are insoluble in said liquid.
20. The colloidal suspension as recited in claim 11 wherein said
nanoparticles are an organic material.
Description
RELATED APPLICATIONS
[0001] This application is a divisional of U.S. application Ser.
No. 12/951,496, filed Nov. 22, 2010, which claims the benefit of
U.S. provisional application Ser. No. 61/302,984 filed Feb. 10,
2010.
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH
[0002] NONE
TECHNICAL FIELD
[0003] This invention relates generally to use of ultrafast pulsed
laser ablation to generate stable hydrocolloids of nanoparticles
having an average diameter of 100 nanometers or less from organic
compounds.
BACKGROUND
[0004] Most sugars are highly soluble in water, but not all solid
organic compounds can be dissolved in water with reasonable
solubility. It is highly desirable to dissolve many solid organic
compounds in water, or to disperse solid organic compounds into
water to form a stable hydrocolloid. It would be most beneficial to
create a method that was applicable to the widest variety of
organic solids. Curcumin,
1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione, is a
natural yellow-orange dye extracted from the rhizomes of Curcuma
longa L. and it has a variety of biological activities and
pharmacological actions. Unfortunately, curcumin is not water
soluble and that limits its' effective bioavailability in many
systems. Many attempts have been made to disperse curcumin into
water to improve its bioavailability. A self-microemulsifying drug
delivery system comprising a microemulsion of curcumin with oils
and surfactants was reported to improve the solubility of curcumin
in water. Jing Cui, Bo Yu, Yu Zhao, Weiwei Zhu, Houli Li, Hongxiang
Lou, Guangxi Zhai, "Enhancement of oral absorption of curcumin by
self-microemulsifying drug delivery systems", International Journal
of Pharmaceutics Vol. 371, 148-155, 2009. A curcumin-phospholipid
complex was reported to greatly increase both the bioavailability
and the formation of metabolites as compared to unformulated
curcumin. T. H. Marczylo, R. D. Verschoyle, D. N. Cooke, P.
Morazzoni, W. P. Steward, A. J. Gescher, "Comparison of systemic
availability of curcumin with that of curcumin formulated with
phosphatidylcholine", Cancer Chemother. Pharmacol., Vol. 60,
171-177, 2007. A polymeric nanoparticle-encapsulated curcumin,
nicknamed "nanocurcumin", was also reported as a novel strategy to
improve the bioavailability of curcumin. S. Bisht, G. Feldmann, S.
Soni, R. Ravi, C. Karikar, A. Maitra and A. Maitra, "Polymeric
nanoparticle-encapsulated curcumin ("nanocurcumin"): a novel
strategy for human cancer therapy", Journal of Nanobiotechnology,
Vol. 5:3, 2007. All of these methods involve using other chemical
compounds in addition to the desired organic compound, in these
references curcumin, to form a complex having improved
bioavailability and solubility in water.
[0005] Pulsed laser ablation of metal or metal-alloy targets in
liquids is one of the physical methods used to produce metal and
metal-alloy nanoparticles. In this process, a pulsed laser beam is
focused on the surface of a target that is submerged in a liquid.
The ablated material re-nucleates in the liquid and forms
nanoparticles. In recent years, there have been reports of applying
pulsed laser ablation techniques to very small volumes of organic
nanoparticle preparations in which organic microcrystalline powders
suspended in a poor solvent are irradiated with intense laser
pulses, which induce fragmentation of the initial crystals. See for
example, Yoshiaki Tamaki, Tsuyoshi Asahi, and Hiroshi Masuhara,
"Tailoring nanoparticles of aromatic and dye molecules by excimer
laser irradiation", Applied Surface Science, Vol. 168, 85-88, 2000;
Teruki Sugiyama, Tsuyoshi Asahi, and Hiroshi Masuhar, "Formation of
10 nm-sized Oxo(phtalocyaninato)vanadium(IV) Particles by
Femtosecond Laser Ablation in Water", Chemistry Letters Vol.33, No.
6, 724, 2004; and T. Asahi, T. Sugiyama, and H. Masuhara, "Laser
Fabrication and Spectroscopy of Organic Nanoparticles", Accounts of
Chemical Research, Vol. 41, No. 12, 2008. A poor solvent is a
liquid that the target organic material has low to no solubility
in. After a sufficient amount of exposure to the laser beam, the
opaque suspension of organic microcrystalline powders is converted
into a transparent colloidal suspension. This laser ablation
approach appears to convert organic microcrystalline powders
directly into stable nanocolloidal suspensions without additives
and chemicals. All of the results reported to date have been
conducted in a cuvette with a total volume of 3 milliliters, and it
is difficult to scale up from this small volume to mass production
of organic nanoparticles with this laser ablation approach.
Obviously, the pulsed laser ablation of an organic microcrystalline
powder suspension in a fixed volume small cuvette cannot maintain a
constant efficiency of generation of organic nanoparticles because
of the decreasing amount of microcrystalline powder available
during the ablation process. Similar results were also reported by
several other groups, see for example I. Elaboudi, S. Lazare, C.
Belin, D. Talaga. And C. Labrugere, "From polymer films to organic
nanoparticles suspensions by means of excimer laser ablation in
water", Appl. Phys. A, Vol 93, 827-831, 2008 and R. Yasukuni, M.
Sliwa, J. Hofkens, F. C. De Schryver, A. Herrmann, K. Mullen, and
T. Asahi, "Size-Dependent Optical Properties of Dendronized
Perylenediimide Nanoparticle Prepared by Laser Ablation in Water",
Japanese Journal of Applied Physics, Vol. 48, 065002, 2009.
[0006] It is desirable to develop a method for formation of
nanoparticles from organic compounds that are poorly soluble in
water and other liquids to increase their bioavailability and
usefulness in biological systems. In addition, it would be useful
to develop a production method for organic nanoparticles that
avoids coagulation, eliminates any requirement for a stabilizing
agent, and that provides for rapid throughput and scale up to mass
production levels.
SUMMARY OF THE INVENTION
[0007] In general terms, this invention provides a method and
system for producing chemically pure and stable colloidal
suspensions of nanoparticles from organic compounds using laser
ablation. The method comprises the steps of generating a high
repetition rate ultrafast pulsed laser beam; providing an organic
compound target and irradiating the organic compound target with
the pulsed laser beam, the target positioned in a liquid that is
substantially transparent at a wavelength of the pulsed laser beam,
the irradiation generating a nanoparticle suspension of the target
in the liquid by ablation; and producing one or both of a flow of
the liquid relative to a surface of the target and relative motion
between the pulsed laser beam and the target. The method and system
are highly efficient and are capable of high production rates for
organic nanoparticle colloidal suspensions. The colloidal
suspensions are stable at 25.degree. C. for at least one week in
the absence of any stabilizing agents. In the present specification
and claims the terms "nanoparticle" or "nanoparticles" with respect
to particles produced according to the present invention means
particles with an average diameter of 100 nanometers or less. A
poor solvent is defined as a liquid wherein the target organic
material has a very low solubility if any solubility at all.
[0008] These and other features and advantages of this invention
will become more apparent to those skilled in the art from the
detailed description of a preferred embodiment. The drawings that
accompany the detailed description are described below.
BRIEF DESCRIPTION OF THE DRAWINGS
[0009] FIG. 1 schematically illustrates a laser-based system for
producing organic nanoparticles in a liquid according to the
present invention;
[0010] FIG. 2 schematically illustrates an alternative laser-based
system for producing organic nanoparticles in a liquid according to
the present invention;
[0011] FIG. 3 schematically illustrates a laser-based system for
producing organic nanoparticles in a liquid according to the
present invention by ablating a side surface of a cylindrical
target;
[0012] FIG. 4 is a plot of absorption versus wavelength of a
curcumin nanoparticle hydrocolloidal dispersion;
[0013] FIG. 5 shows the absorption spectra of a solution of pure
curcumin powder dissolved in methanol and the spectra of a curcumin
nanoparticle hydrocolloidal prepared according to the present
invention mixed with methanol;
[0014] FIG. 6 is a transmission electron microscope (TEM) image of
a dried sample of a drop of a curcumin nanoparticle hydrocolloidal
prepared according to the present invention on a TEM sampling
grid;
[0015] FIG. 7, panel (a), is a mass spectrum of a pure curcumin
powder sample and FIG. 7, panel (b), is a mass spectrum of a
curcumin nanoparticle hydrocolloidal sample prepared according to
the present invention; and
[0016] FIG. 8 is a plot of efficiency of nanoparticle production
according to the present invention versus laser repetition
rate.
DETAILED DESCRIPTION OF THE INVENTION
[0017] The present invention is directed toward a laser system for
producing stable nanoparticle colloidal suspensions from organic
materials using an ultrafast pulsed laser ablation process.
[0018] FIG. 1 schematically illustrates a laser-based system for
producing organic nanoparticles in a liquid in accordance with the
present invention. In one embodiment a laser beam 1 is received
from a ultrafast pulse source, not shown, and focused by a lens 2.
The source of the laser beam 1 can be any suitable ultrafast pulsed
laser source capable of providing a pulse duration, repetition rate
and/or power level as discussed below. The focused laser beam 1
then passes from the lens 2 to a guide mechanism 3 for controlling
movement of the laser beam 1. The guide mechanism 3 can be any of
those known in the art including, by way of example only,
piezo-mirrors, acousto-optic deflectors, rotating polygons,
vibrating mirror, and prisms. Preferably the guide mechanism 3 is a
vibrating mirror 3 to enable controlled and rapid movement of the
focused laser beam 1. The guide mechanism 3 directs the focused
laser beam 1 at a target 4. In one embodiment, the target 4 is a
compressed pellet of an organic compound that is being converted
into nanoparticles. The compressed pellet can be formed from a
variety of powder sources of the organic material. It is preferred
to begin with a powdered source of the organic compound that has an
average particle size of from submicron to millimeter (mm) size
depending on the softness of the starting powder, preferably from
submicron to submillimeter size. The powdered source material can
then be compressed into a pellet using a mold and pressure. The
pressures used depend on the starting material, but the target 4
pellet must be self sustaining and able to maintain integrity in a
container 7 with a flow of a liquid 5 as described below. The size
of the compressed target 4 is larger than 1 mm in at least one
dimension. Alternatively, the target 4 can be another source of the
organic compound material such as: a film of the organic compound
that has been deposited onto a substrate; a bulk material of an
organic compound with at least one dimension that is larger than 5
mm; a stream of the bulk organic compound which has been ejected
from a nozzle into the liquid 5; or a paste of the bulk organic
compound that has been introduced into the liquid 5. Any of these
can serve as the target 4 material in the present invention. At
least a portion of the target 4 is in contact with the liquid 5,
preferably the target 4 is submerged a distance of from several
millimeters to preferably less than 1 centimeter below the surface
of a liquid 5. Preferably, the target 4 is positioned in a
container 7 having a removable glass window 6 on top of the
container 7. An O-ring type of seal 8 is placed between the glass
window 6 and the top of the container 7 to prevent the liquid 5
from leaking out of the container 7. The container 7 includes an
inlet 12 and an outlet 14 so the liquid 5 can be passed over the
target 4 and so that it can be re-circulated. The container 7 is
optionally placed on a motion stage 9 that can produce
translational motion of the container 7 and movement of the liquid
5. Flow of the liquid 5 is used to carry generated nanoparticles 10
out of the container 7 to be collected elsewhere. The flow of
liquid 5 over the target 4 also cools the laser focal volume. The
flow rate and volume of liquid 5 should be sufficient to fill the
gap between the target 4 and the glass window 6 as shown. In
addition, it must be sufficient to prevent any gas bubbles
generated during the laser ablation from staying on the glass
window 6. The liquid 5 can be any liquid that is largely
transparent to the wavelength of the laser beam 1 and that
preferably is a poor solvent for the target material 4. In one
embodiment, the liquid 5 is deionized water, preferably having a
resistivity of greater than 0.05 MOhm.cm, and more preferably
greater than 1 MOhmcm.
[0019] The ultrafast pulsed laser beam 1 preferably has a pulse
duration of 500 picoseconds or less, preferably from about 10
femtoseconds to 500 picoseconds, more preferably from 10
femtoseconds to 200 picoseconds, and most preferably from 100
femtoseconds to 10 picoseconds. The pulse repetition rate is
preferably from 1 Hz to 100 MHz, more preferably from 10 kHz to 10
MHz, and most preferably from 100 kHz to 5 MHz. A preferred
wavelength is about 1045 nanometers, however any suitable
wavelength of from about 400 nanometers to 4000 nanometers may be
used. At a wavelength of 1045 nanometers a layer of water of a few
millimeters in thickness over the target 4 has a negligible
absorption at this wavelength. Preferably the laser beam 1 has a
pulse energy in the range of about 1 nano-Joules to 10 mili-Joules,
more preferably in the range from 100 nano-Joules to 10
micro-Joules for generation of nanoparticles 10. Preferably the
laser beam 1 has a laser fluence at the focus spot on the surface
of target 4 in the range of from about 100 micro-Joules/cm.sup.2 to
100 Joules/cm.sup.2, more preferably from 10 milli-Joules/cm.sup.2
to 5 Joules/cm.sup.2.
[0020] In one embodiment the guide mechanism 3 is a vibrating
mirror 3 that is configured for fast rastering or other movement of
the laser beam 1 on the surface of the target 4. The vibration
frequency of mirror 3 is preferably 10 Hz or greater and preferably
it has an angular amplitude of 0.1 mrad or greater and more
preferably of 1.0 mrad or greater, such that a rastering speed on
the surface of the target 4 is 0.01 meters per second or greater
and most preferably 0.1 meters per second or greater. Such a mirror
3 can be a piezo-driven mirror, a galvanometer mirror, or other
suitable apparatus for movement of the laser beam 1.
[0021] In one embodiment, flow of the liquid 5 through the
container 7 is carried out by a circulation system, with a flow
speed preferably of 1.0 milliliter per second or greater and more
preferably of 10.0 milliliter per second or greater. Flow of liquid
5 is necessary to uniformly distribute the generated nanoparticles
10 in the liquid 5 and to remove them from the container 7. It is
preferred to maintain a sufficient volume of the liquid 5 to avoid
any fluctuations in the thickness of liquid 5 above the target 4.
If the liquid 5 thickness varies it can change the optical path
properties of the laser beam 1 and cause a broader distribution of
sizes of the generated nanoparticles 10. The optical window 6 above
the flowing liquid 5 helps to keep a constant thickness of liquid 5
above the target 4. When a circulation system is not available,
introducing lateral vibration movement, for example perpendicular
to the laser beam 1, as indicated in FIG. 1, to the motion stage 9
can also cause liquid 5 flow locally across the ablation spot. The
motion stage 9 preferably has a vibration frequency of several Hz
and an amplitude of several millimeters. A shaker can also be used
to circulate the liquid 5, wherein the circular movement of the
shaker causes the liquid 5 in the container 7 to have a circular
movement too, therefore the organic nanoparticles 10 can distribute
evenly in the liquid 5. With either of these two methods of
circulating the liquid 5, the glass window 6 is not necessary;
however, the use of either will introduce non-uniformity into the
thickness of the liquid 5 above the target 4 and will cause a
broader size distribution of the nanoparticles 10.
[0022] The present invention provides a system and method for
formation of stable and chemically pure nanoparticle colloidal
suspensions from organic compounds. By stable it is meant that the
hydrocolloidal, if produced in water, or colloidal suspension if
produced in another liquid is stable with no aggregation of the
particles after storage at 25.degree. C. for at least 7 days and
more preferably stable for at least 2 months under these
conditions. By chemically pure it is meant that the colloidal
suspension is composed only of the organic materials found in the
target 4 and the liquid 5 from which the colloidal suspension is
derived. There is no need for added stabilizing agents or surface
active agents to maintain the colloid in a stable state. The
present inventors have discovered that through proper control of
laser parameters including pulse duration, pulse energy, pulse
repetition rate, and movement of the laser beam 1 over the target 4
such stable nanoparticle colloidal suspensions can be produced.
Both the laser beam 1 movement rate and the liquid 5 flow rate can
be used to aid the process by controlling heat accumulation derived
from the preferred high pulse repetition rates used in the present
invention.
[0023] In the present invention ultrashort pulse widths are
preferred. It is preferred that the pulse width or pulse duration
range from 10 femtoseconds to 200 picoseconds and more preferably
from 100 femtoseconds to 10 picoseconds. These short duration
pulses are believed to enhance ablation efficiency because of a
very high peak power and a small heat- affected zone at the
ablation site.
[0024] Previous studies of laser ablation to produce nanoparticles
from metal and metal oxides have found that low pulse energy, more
precisely a low laser fluence at or near the ablation threshold is
preferred for nanoparticle generation from these inorganic target
materials. See for example, B. Liu, Z. D. Hu, Y. Che, "Ultrafast
sources: ultrafast lasers produce nanoparticles", Laser Focus
World, Vol. 43, 74 (2007) and B. Liu, Z. D. Hu, Y. Che, Y. B. Chen,
X. Q. Pan, "Nanoparticle generation in ultrafast pulsed laser
ablation of nickel", Applied Physics Letters, Vol. 90, 044103
(2007). In these studies from metal substrates it was found that
the ablated material existed predominantly in the form of
nanoparticles with a narrow size distribution. A U.S. patent
application Ser. No. 11/712,924 filed on Mar. 2, 2007 and published
on Jan. 10, 2008 as U.S. publication No. 2008/0006524 also teaches
a method of generating nanoparticles from metals and metal oxides
in a vacuum and ambient gas and depositing them on a substrate. The
inventors have found that a low pulse energy near the ablation
threshold is also preferred for formation of organic nanoparticle
colloids. It is preferred for the present invention that the pulses
have a pulse energy of from 1 nano-Joules to 10 mili-Joules, more
preferably from 100 nano-Joules to 10 micro-Joules.
[0025] The present inventors have discovered that a high pulse
repetition rate is very beneficial for producing nanoparticles
according to the present invention from organic source material. A
preferred pulse repetition rate is in the range of from 1 Hz to 100
MHz, more preferably 10 kHz to 10 MHz and most preferably 100 kHz
to 5 MHz. These high repetition rates are beneficial for at least
three reasons. First, these rates produce a multiple pulse effect
in high repetition rate pulsed laser ablation. With a repetition
rate of 100 kHz or greater, for example, the pulse separation is 10
microseconds or less. This period of time is short enough that the
ablated material, before drifting away from the laser focal volume,
will receive multiple laser pulses and become highly charged. The
inventors discovered stable nanoparticle colloids can be made at
such high repetition rates without adding additional stabilizing
chemical agents because of this charging. Second, when the ablation
process comprises multiple pulses of the ablated material,
fragmentation of initially larger particles can occur, resulting in
a final size distribution predominated by nanoparticles. Finally,
the high repetition rate leads to a high production rate of
nanoparticles.
[0026] The inventors have also discovered that fast rastering of
the laser beam 1 during the ablation process is beneficial in
conjunction with the high repetition rate to produce nanoparticles
from organic sources. A preferred rastering rate is 0.01 meters per
second or greater and more preferred is a rastering rate of 0.1
meters per second or greater. Without such fast rastering of the
laser beam 1, the stream of nanoparticles 10 produced by the
leading laser pulses will eventually block the subsequent laser
pulses by scattering and absorption of the laser beam 1. More
importantly, accumulated heating of the liquid 5 due to the high
repetition rate can also induce coagulation of the nanoparticles
10.
[0027] In addition to the laser parameters described above, the
inventors have found that movement of the liquid 5 is also useful
in making stable nanoparticle colloids. This is primarily because a
dispersed colloidal suspension of nanoparticles 10 in a liquid 5
such as water is essentially in a metastable state, i.e., a
kinetically stable state and not a thermodynamically stable state.
Flow of the liquid 5 during production helps to reduce a
nanoparticle's 10 thermal movement, which may overcome the kinetic
barrier to coagulation. Preferably the liquid 5 flow rate is 1
milliliter per second or greater, more preferably 10 milliliter per
second or greater. A fast rastering of the laser beam 1 is also
beneficial in reducing a nanoparticle's 10 thermal motion.
[0028] FIG. 2 schematically illustrates an alternative laser-based
system for producing organic nanoparticles in a liquid in
accordance with the present invention. In this embodiment the laser
beam 1 is received from a ultrafast pulse source, not shown, and
focused by the lens 2. The source of the laser beam 1 can be any
suitable pulsed laser source capable of providing a pulse duration,
repetition rate and/or power level as discussed above. The focused
laser beam 1 then passes from the lens 2 to the guide mechanism 3
for controlling movement of the laser beam 1. The guide mechanism 3
can be any of those known in the art including by way of example
piezo-mirrors, acousto-optic deflectors, rotating polygons,
vibrating mirror, and prisms. Preferably the guide mechanism 3 is a
vibrating mirror 3 to enable controlled and rapid movement of the
focused laser beam 1. The guide mechanism 3 directs the focused
laser beam 1 at the target 4. Preferably the target 4 is a
compressed pellet of the organic compound that is being converted
into nanoparticles. The compressed pellet can be formed from a
variety of powder sources of the organic material. The powdered
source material is then compressed into a pellet using a mold and
pressure. The bottom of the container 7 serves as glass window 6 to
allow the focused laser beam 1 pass through to ablate the organic
compound target 4. The target can be submerged into the liquid 5,
or the bottom of target 4 can just touch a top surface of the
liquid 5. The distance between the bottom of target 4 and glass
window 6 can be from several millimeters to preferably less than 1
centimeter. The container 7 includes the inlet 12 and the outlet 14
so the liquid 5 can be passed over the target 4 and so that it can
be re-circulated. Flow of the liquid 5 is used to carry generated
nanoparticles 10 out of the container 7 to be collected elsewhere.
The flow of liquid 5 over the target 4 also cools the laser focal
volume. The liquid 5 can be any liquid that is largely transparent
to the wavelength of the laser beam 1 and that preferably is a poor
solvent for the target material 4. In one embodiment the target 4
can be mounted on a rotating mechanism and spin during the ablation
with the spin speed from several revolutions per minute to a
several hundred revolutions per minute as shown by the arrow in the
figure. As the target 4 rotates, some of the liquid described as
the hydrodynamic boundary layer is dragged by the spinning Liquid
flows up, perpendicular to the target 4, from the bottom to replace
the boundary layer. The sum results are a laminar flow of liquid 5
towards and across the target 4, and distribution of the generated
nanoparticles 10 into liquid 5. This also prevents any gas bubbles
generated during the laser ablation from staying on the target
4.
[0029] FIG. 3 schematically illustrates another alternative
laser-based system for producing organic nanoparticles in a liquid
in accordance with the present invention. In this embodiment the
laser beam 1 is received from a ultrafast pulse source, not shown,
and focused by the lens 2. The source of the laser beam 1 can be
any suitable pulsed laser source capable of providing a pulse
duration, repetition rate and/or power level as discussed above.
The focused laser beam 1 then passes from the lens 2 to the guide
mechanism 3 for controlling movement of the laser beam 1. The guide
mechanism 3 can be any of those known in the art including by way
of example piezo-mirrors, acousto-optic deflectors, rotating
polygons, vibrating mirror, and prisms. Preferably the guide
mechanism 3 is a vibrating mirror 3 to enable controlled and rapid
movement of the focused laser beam 1. The guide mechanism 3 directs
the focused laser beam 1 at the target 4. Preferably the target 4
is a compressed cylinder of the organic compound that is being
converted into nanoparticles. The compressed cylinder can be formed
from a variety of powder sources of the organic material. The
powdered source material is then compressed into a cylinder using a
mold and pressure. The bottom of the container 7 serves as glass
window 6 to allow the focused laser beam 1 to pass through and to
ablate the organic compound target 4. The target 4 can be submerged
into liquid 5, or the side surface of target 4 can just touch the
top surface of liquid 5. The distance between the side surface of
target 4 and glass window 6 can be from several millimeters to
preferably less than 1 centimeter. The container 7 includes the
inlet 12 and the outlet 14 so the liquid 5 can be passed over the
target 4 and so that it can be re-circulated. Flow of the liquid 5
is used to carry generated nanoparticles 10 out of the container 7
to be collected elsewhere. The flow of liquid 5 over the target 4
also cools the laser focal volume. The liquid 5 can be any liquid
that is largely transparent to the wavelength of the laser beam 1
and that preferably is a poor solvent for the target material 4. In
one embodiment the target 4 is mounted on a rotating mechanism and
rotates during the ablation with the rotation speed from several
revolutions per minute to a several hundred revolutions per minute
as shown by the arrow in the figure. In this layout, the
nanoparticles 10 are generated at the side surface of the
cylindrical organic compound target 4 instead of at the end surface
of the cylindrical target. As the target 4 rotates, it will help to
distribute generated nanoparticles 10 into liquid 5, and prevent
any gas bubbles generated during the laser ablation from staying on
the target 4.
[0030] In a first experiment curcumin powder, purchased from Sigma
Aldrich, was used as the organic source material. The curcumin
powder was formed into a pellet of target material by compression
in a 0.5 inch in diameter mold using three tons of pressure. The
curcumin pellet was then ablated according to the present invention
using deionized water as the liquid. The flow rate of the liquid in
the container was about 80 milliliters per second. The curcumin
pellet was ablated using an ultrafast pulsed laser having a
wavelength of 1045 nanometers, using a pulse duration of 500
femtoseconds, a pulse energy of 1 microJoules, a power of 1 W and a
pulse repetition rate of 1 MHz. The laser focus spot size was about
30 micrometers in diameter and the fluence is calculated at about
0.14 Joules/cm.sup.2. The frequency of the vibrating mirror was 50
Hz with a 4 millimeter trace for 0.4 meters per second. The
obtained curcumin nanoparticle hydrocolloidal suspension had a
yellow color. FIG. 4 shows an absorption spectrum of the curcumin
nanoparticle hydrocolloidal which is represented by an absorption
peak centered at about 420 nanometers. The hydrocolloidal contains
some large particles as evidenced by the spread of the peak and the
background absorbance of the curve. The y-axis is the absorption
and the x-axis is the wavelength. Because curcumin does not
dissolve in water there is no curcumin in water spectrum that can
be used as a reference to compare to the hydrocolloidal curcumin
nanoparticles.
[0031] Curcumin is dissolvable in methanol, thus the starting
curcumin powder was dissolved in methanol at a concentration of
2.5.times.10.sup.-5 M to serve as a standard. In addition, 0.1
milliliters of the curcumin nanoparticle hydrocolloidal prepared
according to the present invention was mixed with 1.0 milliliters
of methanol. The mixture of prepared nanoparticle hydrocolloidal
and methanol was a clear yellow colored solution as was the
solution of curcumin powder dissolved in methanol. FIG. 5 shows the
absorption spectra of each curcumin methanol solution. The solid
line trace is the hydrocolloidal sample prepared according to the
present invention. The dotted line trace is the curcumin standard.
As can be seen the two spectra are virtually identical with a major
peak at 420 nanometers indicating the existence of curcumin in the
hydrocolloidal sample. The trace with the slightly higher peak at
420 nanometers is from the hydrocolloidal sample prepared according
to the present invention. The identical nature of the spectra
indicates that ablation of a curcumin pellet in water using a low
energy ultrafast pulsed laser according to the present invention
does not destroy the curcumin structure, instead curcumin
nanoparticles are generated and disperse into water forming a
stable curcumin nanoparticle hydrocolloidal suspension.
[0032] It was found that ablation of the curcumin pellet target in
water using higher pulse energies generated larger particles and
these larger particles tended to precipitate from the
hydrocolloidal suspension. Thus, as the pulse energy is increased
the number of larger particles increases. These large particles can
be easily separated from the hydrocolloidal suspension either by
filtration or by centrifugal separation at 2000 rpm for 3 to 5
minutes. Using filter paper to retain the large curcumin aggregates
enables them to be separated from the curcumin hydrocolloid. The
filter paper is then washed with methanol to dissolve the retained
aggregates. For example, Fisher P8 paper with a particle retention
size of 25 microns can be used. Using the pure curcumin powder
dissolved in methanol an absorbance at 420 nm standard curve can be
generated. Then the curcumin level can be determined in both the
nanoparticle hydrocolloid and in the filtrate washed off of the
filter. Then the efficiency of using laser ablation to generate
curcumin nanoparticles can be determined. It was found that the
efficiency of production of nanoparticles increased as the laser
pulse energy was decreased. FIG. 8 shows the efficiency of
producing nanoparticles versus the laser repletion rate. The total
power of the laser was fixed at 1 Watt; therefore, an increase of
repetition rate represents a decrease of pulse energy. The
efficiency was calculated from the amount of nanoparticles in
colloidal solution and the amount of particles retained on the
filter paper as a percentage of the total. The amounts in each were
determined from the absorbance at 420 nanometers of UV-Vis
absorption curves for colloid/MeOH and filter paper retained
particles dissolved in methanol as described above. If the laser
pulse energy is decreased too much, then the production rate is too
slow. It is possible to compensate for some of the low production
rate at low pulse energies by raising the repetition rate.
[0033] FIG. 6 is a transmission electron microscope (TEM) image of
curcumin nanoparticles generated from a pellet of curcumin in
deionized water according to the present invention. The average
power of the laser used was 0.9W with a repetition rate of 100 kHz,
pulse energy of 9 micro-Joules, wavelength of 1045 nanometers,
pulse duration of 500 femtoseconds. The laser beam had a focal spot
diameter of 50 microns and the raster rate was as described above.
The generated nanoparticle hydrocolloidal suspension was filtered
through Fisher Scientific's P8 filter paper which has a retention
size of 25 microns. A drop of the filtrate was transferred to a TEM
sampling grid and dried. Although the curcumin nanoparticles
aggregate during the drying process, the original nanoparticles are
still recognizable and it can be seen that most have a size of less
than 100 nanometers.
[0034] FIG. 7, panel (a), is the Mass Spectrum (MS) of pure
curcumin starting powder and FIG. 7, panel (b), is the MS of a
curcumin hydrocolloidal sample prepared according to the present
invention. The curcumin hydrocolloidal sample was prepared using
ultrafast laser ablation according to the present invention in a
container with the following laser parameters: 1 Watt of power,
repetition rate of 1 MHz, wavelength of 1045 nanometers, 500
femtosecond pulse duration, and the same raster rate as described
above. The liquid was deionized water. It is observed that the most
intense peaks in both MS tracings are at a mass of 391 for both
standard curcumin and the hydrocolloidal sample, which indicates
that the curcumin molecules are unchanged during the laser ablation
according to the present invention. The major peak at mass 391 can
be assigned to the complex of curcumin, mass 368, and sodium, mass
23. The starting curcumin powder was examined using Energy
Dispersed Spectroscopy and no existence of sodium in the curcumin
powder was found. This indicates that the sodium is introduced into
both samples during the MS process. Despite the appearance of
sodium on the MS for both standard curcumin and the hydrocolloidal
sample, this does not change the fact that laser ablation of the
curcumin pellet in water to form the nanoparticle hydrocolloidal
did not destroy the molecular structure of the curcumin.
[0035] While the present invention has been illustrated using
curcumin as the organic target material and deionized water as the
liquid it is much more broadly applicable. Any other organic
material that can be formed into a target pellet could be used as
the target material. Alternatively, as discussed above, the target
can be another source of the organic compound material such as: a
film of the organic compound that has been deposited onto a
substrate; a bulk material of an organic compound with at least one
dimension that is larger than 5 mm; a stream of the bulk organic
compound which has been ejected from a nozzle into the liquid; or a
paste of the bulk organic compound that has been introduced into
the liquid. Any of these can serve as the target material in the
present invention. In addition, liquids other than deionized water
could be used depending on the desired colloidal suspension.
[0036] The foregoing invention has been described in accordance
with the relevant legal standards, thus the description is
exemplary rather than limiting in nature. Variations and
modifications to the disclosed embodiment may become apparent to
those skilled in the art and do come within the scope of the
invention. Accordingly, the scope of legal protection afforded this
invention can only be determined by studying the following
claims.
* * * * *