U.S. patent application number 14/724440 was filed with the patent office on 2015-12-03 for laser-directed microcavitation.
The applicant listed for this patent is INSTITUT NATIONAL D'OPTIQUE. Invention is credited to Pascal DELADURANTAYE, Ozzy MERMUT.
Application Number | 20150342678 14/724440 |
Document ID | / |
Family ID | 54700452 |
Filed Date | 2015-12-03 |
United States Patent
Application |
20150342678 |
Kind Code |
A1 |
DELADURANTAYE; Pascal ; et
al. |
December 3, 2015 |
LASER-DIRECTED MICROCAVITATION
Abstract
Methods and systems for the controlled generation of
microcavitation bubbles in a medium having a liquid phase are
generally provided. Laser pulses having a time-dependent pulse
parameter controllable over their duration are generated. The
medium is irradiated with the laser pulses with a radiant exposure
sufficient to initiate microcavitation within the medium during
each laser pulse. The time-dependent pulse parameter of each laser
pulse is controlled according to a generally positive variation
over the pulse duration such that the medium absorbs a greater
quantity of energy from the laser pulse at an end of the pulse
duration than at a beginning thereof. Such methods and systems may
be used for various applications such as biology, medicine or
material processing.
Inventors: |
DELADURANTAYE; Pascal;
(Quebec, CA) ; MERMUT; Ozzy; (Quebec, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
INSTITUT NATIONAL D'OPTIQUE |
Quebec |
|
CA |
|
|
Family ID: |
54700452 |
Appl. No.: |
14/724440 |
Filed: |
May 28, 2015 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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62003740 |
May 28, 2014 |
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Current U.S.
Class: |
606/2.5 ;
250/492.1; 435/173.5; 435/29; 435/460; 606/11; 606/5; 606/6;
606/9 |
Current CPC
Class: |
A61B 2018/00577
20130101; A61B 2017/00185 20130101; A61B 2018/2035 20130101; A61B
2018/00535 20130101; A61B 2017/00159 20130101; A61B 2018/2255
20130101; G01N 33/5005 20130101; A61B 2018/206 20130101; A61B 18/20
20130101; A61F 9/008 20130101; C12N 13/00 20130101; A61B 2018/20355
20170501; A61F 9/00814 20130101; A61B 2018/00511 20130101; A61B
18/22 20130101 |
International
Class: |
A61B 18/20 20060101
A61B018/20; G01N 33/50 20060101 G01N033/50; C12N 13/00 20060101
C12N013/00; A61F 9/008 20060101 A61F009/008 |
Claims
1. A method for the controlled generation of microcavitation
bubbles in a medium having a liquid phase, comprising: generating
one or more laser pulses, each laser pulse having a pulse duration
and having a time-dependent pulse parameter controllable over the
pulse duration; irradiating the medium with the laser pulses with a
radiant exposure sufficient to initiate microcavitation within the
medium during each laser pulse; and controlling the time-dependent
pulse parameter of each laser pulse according to a generally
positive variation over the pulse duration such that the medium
absorbs a greater quantity of energy from the laser pulse at an end
of the pulse duration than at a beginning thereof.
2. The method according to claim 1, wherein the time-dependent
pulse parameter is an amplitude of the laser pulses.
3. The method according to claim 1, wherein the time-dependent
pulse parameter is a spectral content of the laser pulses.
4. The method according to claim 1, wherein the time-dependent
pulse parameter is a spatial profile of the laser pulses.
5. The method according to claim 1, wherein the generally positive
variation of the time-dependent pulse parameter defines a
sawtooth-like shape having a positive slope.
6. The method according to claim 1, wherein the generally positive
variation of the time-dependent pulse parameter defines first phase
of regularly increasing amplitude, followed by a second phase of
sharply decreasing amplitude.
7. The method according to claim 1, wherein the generally positive
variation of the time-dependent pulse parameter defines a low
initial step followed by a sharp increased amplitude phase and a
sharp decrease amplitude phase, sequentially.
8. The method according to claim 1, wherein the generally positive
variation of the time-dependent pulse parameter defines a sequence
of sub-pulses of gradually increasing peak amplitude.
9. A laser system for generating microcavitation bubbles in a
controlled manner in a medium having a liquid phase, comprising: a
laser pulse generating assembly for generating one or more of laser
pulses, each laser pulse having a pulse duration and a
time-dependent pulse parameter controllable over the pulse
duration, the laser pulses having a radiant exposure sufficient to
initiate microcavitation within the medium during each laser pulse
when impinging on said medium; and a pulse shaping mechanism
configured to control the time-dependent pulse parameter of each
laser pulse according to a generally positive variation over the
pulse duration such that the medium absorbs a greater quantity of
energy from the laser pulse at an end of the pulse duration than at
a beginning thereof.
10. The laser system according to claim 9, wherein the laser pulse
generating assembly comprises a seed light source and at least one
optical amplifier.
11. The laser system according to claim 9, wherein the
time-dependent pulse parameter is one of an amplitude, a spectral
content or a spatial profile of the laser pulses.
12. The laser system according to claim 9, wherein the pulse
shaping mechanism comprises a digital pulse shaping module
providing control signals to the laser pulse generating
assembly.
13. A method for selectively altering an organism having a liquid
phase comprising the step of: generating microcavitation bubbles in
said organism in a controlled manner by: generating one or more,
each laser pulse having a pulse duration and having a
time-dependent pulse parameter controllable over the pulse
duration; irradiating the organism with the laser pulses with a
radiant exposure sufficient to initiate microcavitation within the
organism during each laser pulse; and controlling the
time-dependent pulse parameter of each laser pulse according to a
generally positive variation over the pulse duration such that the
organism absorbs a greater quantity of energy from the laser pulse
at an end of the pulse duration than at a beginning thereof.
14. The method according to claim 13, wherein said organism is
selected from the group consisting of: a prokaryotic cell, a
eukaryotic cell and a virus.
15. The method according to claim 14, wherein said organism is
suspended in a fluid.
16. The method according to claim 13, wherein said organism is a
tissue, an organ or an organelle having a liquid phase.
17. The method according to claim 13, carried out in vitro, in vivo
or ex vivo.
18. The method of claim 16, for laser ablation of an organ or a
tissue, tumor destruction, microsurgery, or for selective
photothermolysis.
19. The method of claim 18, for tattoo or hair removal.
20. The method according to claim 17, wherein said irradiating is
carried out in vivo on a tissue, organ, or biological fluid for the
treatment of a disease or a condition necessitating selectively
destroying an affected tissue, organ or biological fluid having a
liquid phase of a subject in need thereof
21. The method of claim 20, wherein said disease or condition is
selected from the group consisting of: kidney stones, bezoars or
gallstones, cancer or an ophthalmologic condition
22. The method of claim 21, wherein said ophthalmologic condition
is selected from: floaters, retinal disease, ametropia, cataracts
and glaucoma.
23. The method of claim 21, for lithotripsy, selective retina
therapy, selective laser trabeculoplasty, refractive surgery,
capsulotomy or laser vitreolysis.
24. A method for selectively altering a cell having a liquid phase,
comprising the step of injecting a light absorber in said cell,
irradiating said light absorber with laser pulses produced by the
laser system of claim 9, so as to increase permeability of said
cell.
25. The method of claim 24, further comprising transfecting a
genetic material or a drug to said cell.
26. A method for detecting a presence of a light absorber in a
medium having a liquid phase, said method comprising the step of
irradiating said light absorber with laser pulses produced by the
laser system of claim 9, thereby generating detectable
microcavitation bubbles in said medium indicative of the presence
of the light absorber.
27. The method of claim 26, wherein the light absorber comprises a
nanoparticle or a dye.
28. A method for processing a material using microcavitation, the
material comprising a medium having a liquid phase or being in
contact with a medium having a liquid phase, said method comprising
the step of irradiating said medium with laser pulses produced by
the laser system of claim 9.
Description
[0001] This application claims benefit of U.S. Ser. No. 62/003,740,
filed 28 May 2014 and which application is incorporated herein by
reference. To the extent appropriate, a claim of priority is made
to the above disclosed application.
TECHNICAL FIELD
[0002] The present invention relates to microcavitation techniques
and more particularly concerns the use of laser pulse shaping to
control the generation of microbubbles in a medium having a liquid
phase.
BACKGROUND
[0003] Laser-directed microcavitation is a photomechanical
interaction involving the generation of vapor bubbles within a
medium possessing a liquid phase, upon absorption of pulsed laser
energy by the medium. The medium can be homogeneous comprising only
the liquid phase, or can be heterogeneous and comprises the liquid
phase mixed with one or more solid phases. For laser pulse
durations shorter than a few microseconds, microcavitation can be a
dominant mechanism causing alterations of the medium in which it is
taking place. As laser energy is absorbed by the medium, the medium
temperature rises at a rate that depends on the characteristics of
both the medium and the laser beam. Above a certain threshold
temperature, vaporization of the medium occurs and one or several
vapor bubbles starts to expand. During bubble expansion, the vapor
cools down and the bubble's internal pressure decreases. At some
moment during the process, the bubble's internal pressure is no
longer sufficient to overcome the external pressure, and a maximum
bubble volume is reached as the expansion stops. A contraction
phase follows, after which the bubble disappears. Following the
first expansion-collapse cycle, additional oscillations with
decreasing maximum bubble volumes can be observed.
[0004] In general, the total volume of medium potentially altered
by laser-directed microcavitation is determined by two principal
contributions. A first contribution involves thermally-induced
effects, for which the affected volume is determined by the
diffusion of heat within the medium as a result of the absorption
of laser energy. A second contribution includes
mechanically-induced alterations originating from stresses
developing in the medium as the microcavitation bubbles expand and
collapse. In the latter case, the mechanically-affected volume of
medium around the bubble's center is at least as large as the
maximum volume of the cavitation bubble.
[0005] An example of a heterogeneous medium is the cytoplasm of
cells, particularly pigmented cells where the pigments absorb the
energy. Selective Retina Therapy (SRT) is an example of an
application which may involve or exploit laser-directed
microcavitation. The absorption of laser light by melanin pigments
synthetized in the melanosomes, which are membrane-bound organelles
of the Retinal Pigment Epithelium (RPE) cells, can be exploited to
selectively alter these cells. For such applications, it is often
critical and difficult to predict and control the total volume of
medium affected thermally and photomechanically. Currently,
documented work examining the influence of time-domain irradiation
parameters on the spatial extent of thermal and photomechanical
alterations produced by microcavitation has mainly focused on the
impact of the laser pulse duration. For example, it is well-known
that as the pulse duration is reduced, the threshold radiant
exposure to initiate microcavitation is also reduced because of
improved thermal confinement (R. Brinkmann et al., "Selective RPE
photodestruction: mechanism of cell damage by pulsed-laser
irradiance in the ns to .mu.s time regime", Proc. SPIE 3601,
Laser-Tissue Interaction X: Photochemical, Photothermal, and
Photomechanical, (Jun. 14, 1999)). As the pulse duration becomes
short compared to the characteristic heat diffusion time within the
medium, steeper temperature gradients can be locally produced
because heat has less time to diffuse away during exposure to the
pulse. The critical temperature for bubble formation can thus be
reached with less energy delivered to the medium, because less
energy escapes from the absorption centers present in the medium
during exposure to the pulse. Short pulses are therefore more
attractive than long pulses from a purely thermal point of view,
because microcavitation can be triggered with lower energy levels
of laser energy and with better spatial confinement of the
thermally-induced alterations.
[0006] On the other hand, it is also well-known that as the pulse
duration is shortened, the vaporization tends to become more
explosive (J. Neumann and R. Brinkmann, "Microbubble dynamics
around laser heated microparticles", in Therapeutic Laser
Applications and Laser-Tissue Interactions, R. Steiner, ed., Proc.
SPIE 5142, paper 5142.sub.--82 (Oct. 17, 2003)). With shorter
pulses, the maximum bubble volume increases more rapidly with
radiant exposure, making the control of the bubble volume more
challenging. Therefore, the benefit of using shorter pulses from a
thermal perspective can be cancelled by the risk of losing control
over the volume of medium altered photomechanically. As a
consequence, trade-offs involving longer pulse durations have been
so far necessary to mitigate this risk, which lead to sacrifices on
the thermal confinement.
[0007] A closer look at the distribution of melanosomes inside RPE
cells is instructive for understanding the importance of
controlling cavitation bubbles and heat diffusion in SRT
procedures. As illustrated in FIG. 1 (PRIOR ART), melanosomes tend
to gather on the apical side of RPE, close to the RPE-photoreceptor
interface, and the distance between individual melanosomes and the
photoreceptors can be as small as 1 .mu.m or even in the sub-micron
range. As heat typically diffuses at a rate of roughly 1 .mu.m per
.mu.s in the retina, pulses longer than 1 .mu.s are likely to
induce thermal damages to the fragile photoreceptors. Currently,
SRT procedures rely on Q-switch laser pulses having a duration of
about 1.7 .mu.s, mainly because shorter pulse durations are
considered too dangerous due to the lack of control on the volume
of the cavitation bubbles. For Q-switch pulses having a duration of
1.8 .mu.s, a self-limitation phenomenon of the cavitation bubble
size upon increase of the radiant exposure above the cavitation
threshold has been reported in microcavitation experiments carried
out with suspensions of porcine melanosomes in water (J. Neumann
and R. Brinkmann, "Microbubble dynamics around laser heated
microparticles", in Therapeutic Laser Applications and Laser-Tissue
Interactions, R. Steiner, ed., Proc. SPIE 5142, paper 5142.sub.--82
(Oct. 17, 2003)). These experiments showed that short Q-switch
pulses (e.g. 12 ns duration) produce a rapid increase of the
average bubble size with radiant exposure, whereas for longer
Q-switch pulses (e.g. 1.8 .mu.s) the bubble size remains
essentially constant and small over a certain range of radiant
exposures (FIG. 2).
[0008] A constant bubble volume would be beneficial from a clinical
perspective since bubbles of limited volume can be produced without
a strong dependency over the radiant exposure, which represents a
practical advantage for the clinicians in the context of variable
eye transmission and pigmentation levels from patient to
patient.
[0009] Overall, current techniques of microcavitation are limited
for controlling both types of confinement at the same time. In
applications, this translates into a limited precision for creating
specific, local alterations of the medium. This lack of spatial
resolution can lead to detrimental effects, as a consequence of
collateral alterations created at locations that were not initially
targeted. There is therefore a need for improving precision in such
applications of laser-directed microcavitation.
SUMMARY
[0010] In accordance with one aspect, there is provided a method
for the controlled generation of microcavitation bubbles in a
medium having a liquid phase.
[0011] The method includes generating one or more laser pulses.
Each laser pulse has a pulse duration and time-dependent pulse
parameter controllable over the pulse duration. The method also
includes irradiating the medium with the laser pulses with a
radiant exposure sufficient to initiate microcavitation within the
medium during each laser pulse, and controlling the time-dependent
pulse parameter of each laser pulse according to a generally
positive variation over the pulse duration such that the medium
absorbs a greater quantity of energy from the laser pulse at an end
of the pulse duration than at a beginning thereof.
[0012] In some embodiments the time-dependent pulse parameter may
be the amplitude, the spectral content or the spatial profile of
the laser pulses. The generally positive variation of the
time-dependent pulse parameter may define various shapes, such as:
[0013] a sawtooth-like shape having a positive slope; [0014] first
phase of regularly increasing amplitude, followed by a second phase
of sharply decreasing amplitude; [0015] a low initial step followed
by a sharp increased amplitude phase and a sharp decrease amplitude
phase, sequentially; [0016] a sequence of sub-pulses of gradually
increasing peak amplitude.
[0017] In accordance with another aspect, there is also provided a
laser system for generating microcavitation bubbles in a controlled
manner in a medium having a liquid phase.
[0018] The laser system first includes a laser pulse generating
assembly for generating one or more laser pulses, each laser pulse
having a pulse duration and a time-dependent pulse parameter
controllable over the pulse duration. The laser pulses have a
radiant exposure sufficient to initiate microcavitation within the
medium during each laser pulse when impinging on said medium.
[0019] The laser system further includes a pulse shaping mechanism.
The pulse shaping mechanism is configured to control the
time-dependent pulse parameter of each laser pulse according to a
generally positive variation over the pulse duration such that the
medium absorbs a greater quantity of energy from the laser pulse at
an end of the pulse duration than at a beginning thereof.
[0020] In accordance with yet another aspect, there is provided a
method for selectively altering an organism having a liquid phase
comprising the step of generating microcavitation bubbles in said
organism in a controlled manner by: [0021] generating a plurality
of laser pulses, each laser pulse having a pulse duration and
having a time-dependent pulse parameter controllable over the pulse
duration; [0022] irradiating the organism with the laser pulses
with a radiant exposure sufficient to initiate microcavitation
within the organism during each laser pulse; and [0023] controlling
the time-dependent pulse parameter of each laser pulse according to
a generally positive variation over the pulse duration such that
the organism absorbs a greater quantity of energy from the laser
pulse at an end of the pulse duration than at a beginning
thereof.
[0024] In accordance with yet another aspect, there is provided a
method for selectively altering a cell having a liquid phase,
comprising the step of injecting a light absorber in said cell,
irradiating said light absorber with laser pulses produced by the
laser system above, so as to increase permeability of said
cell.
[0025] There is also provided a method for detecting a presence of
a light absorber in a medium having a liquid phase. The method
includes the step of irradiating said light absorber with laser
pulses produced by the laser system above, thereby generating
detectable microcavitation bubbles in said medium indicative of the
presence of the light absorber.
[0026] Finally, there is also provided a method for processing a
material using microcavitation, the material comprising a medium
having a liquid phase or being in contact with a medium having a
liquid phase, said method comprising the step of irradiating said
medium with laser pulses produced by the laser system above.
[0027] Features and advantages of the invention will be better
understood upon reading of preferred embodiments thereof with
reference to the appended drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0028] FIG. 1 (PRIOR ART) is a schematic representation of the
distribution of melanosomes within RPE cells with respect to the
position of photoreceptors.
[0029] FIG. 2 (PRIOR ART) is a comparison of cavitation bubble
lifetime and diameter above the threshold radiant exposure for two
different Q-switch laser pulse durations, as reported by Neumann
and Brinkmann.
[0030] FIG. 3 (PRIOR ART) shows a Q-switch-like laser pulse shape
having a total duration of 630 ns.
[0031] FIG. 4 shows a sawtooth-like laser pulse shape as may be
used in embodiments, having a total duration of 630 ns.
[0032] FIG. 5 is a graph plotting the average maximum cavitation
bubble volume measured for the pulse shapes of FIGS. 3 and 4,
respectively, as a function of radiant exposure H normalized to the
threshold radiant exposure H.sub.T, for suspensions of bovine
melanosomes in water irradiated at 532-nm wavelength (single-pulse
irradiation).
[0033] FIGS. 6(a) to (c) show the details of the cavitation
dynamics observed in the experiment described in FIG. 5. First row:
pulse formats. Rows 2, 3 and 4: probe transmission for values of
H/H.sub.T of 1.25, 1.50 and 1.87 respectively. Columns (a) and (b)
show two different dynamics observed with the same Q-switch like
pulse format. Column (c): dynamics recorded when using the
sawtooth-like pulse shape.
[0034] FIG. 7 illustrates six (6) examples of pulse shapes that may
be used in embodiments of the invention.
[0035] FIG. 8 illustrates the control of cavitation dynamics
achievable with a pulse format including multiple sub-pulses.
[0036] FIG. 9 schematically illustrates a laser system for
generating microcavitation bubbles according to one embodiment.
[0037] FIG. 10 schematically illustrates a laser system for
generating microcavitation bubbles according to another
embodiment.
DETAILED DESCRIPTION
[0038] In accordance with implementations, the tailoring of laser
pulses is used to provide a better control of laser-directed
microcavitation processes.
[0039] As explained above, laser-directed microcavitation involves
the generation of vapor bubbles within a medium possessing a liquid
phase, upon absorption of laser energy by the medium. The medium
may be affected by both thermally-induced alterations resulting
from heat diffusion within the medium, and by mechanically-induced
alterations originating from stresses developing in the medium as
the microcavitation bubbles expand and collapse. In the description
below, the reference to "alterations" of a medium through
microcavitation may encompass either thermally-induced alterations,
mechanically-induced alterations or both. Particularly, in the case
of biological media (such as, for example, living organisms or
tissue), the medium can be homogeneous or heterogeneous and the
"alterations" may affect the structure or the biological function
of the organism, or both.
[0040] The expression "microcavitation" is typically used to refer
to processes leading to the generation of transient bubbles of
micrometric dimensions, but it will be generally understood that
the use of language such as "microcavitation" or "microbubble" is
not meant to impart any specific size limitations to the physical
phenomena to which the present invention may apply.
[0041] In accordance with some implementations, there is provided a
method for the controlled generation of microcavitation bubbles in
a medium having a liquid phase which generally includes: [0042]
generating one or more laser pulses, each laser pulse having a
pulse duration and having a time-dependent pulse parameter
controllable over the pulse duration; [0043] irradiating the medium
with the laser pulses with a radiant exposure sufficient to
initiate microcavitation within the medium during each laser pulse;
and [0044] controlling the time-dependent pulse parameter of each
laser pulse according to a generally positive variation over the
pulse duration such that the medium absorbs a greater quantity of
energy from the laser pulse at an end of the pulse duration than at
a beginning thereof.
[0045] It will be readily understood that the elements or steps of
the method as presented above are not meant to describe a
consecutive series of event and that they may occur concurrently or
in a different order without departing from the scope of the
invention.
Examples of Applications
[0046] Controlled microcavitation may be of use for several
applications, for example in the biomedical field. Particularly,
when used in the field of biology or medicine, the medium having a
liquid phase may be an organism, particularly a living organism,
that needs to be destroyed, killed, cut, removed or altered
selectively from its immediate surrounding environment (i.e.
healthy tissue/organ, surrounding cells, blood or other biological
fluid, cell culture medium, water, for example potable water or
waste water).
[0047] More particularly, some implementations provide a method for
selectively killing, destroying or altering a living organism
having a liquid phase comprising the step of: generating
microcavitation bubbles in said organism in a controlled manner by:
generating one or more of laser pulses, each laser pulse having a
pulse duration and having a time-dependent pulse parameter
controllable over the pulse duration; irradiating the organism with
the one or more laser pulses with a radiant exposure sufficient to
initiate microcavitation within the medium during each laser pulse;
and controlling the time-dependent pulse parameter of each laser
pulse according to a generally positive variation over the pulse
duration such that the organism absorbs a greater quantity of
energy from the laser pulse at an end of the pulse duration than at
a beginning thereof.
[0048] Such living organism may be a prokaryotic cell, a eukaryotic
cell or a virus, particularly suspended in a biological fluid (such
as blood) or in a cell culture medium. Particularly, the living
organism is a tissue or an organ having a liquid phase. In a
particular aspect, the organism is submitted to the method of the
present invention in vivo, in vitro or ex vivo.
[0049] For example, selective alteration of cells or tissues may be
necessary in ocular laser treatments, such as SRT, for selectively
altering the medium surrounding the melanin pigments, thereby
leading to the alteration (and eventual destruction) of the
melanosomes in retinal epithelium cells.
[0050] As well, nanoparticle-assisted cellular microsurgery may be
useful for tissue or organ resection, in particular for cancer
treatment. Additionally, implementations of the present method and
system may be carried out to produce microbubble-mediated
transfection of drugs or genetic material in cells after
insertion/injection of a light absorber into cells and then
irradiating the absorber to increase cell permeability. The light
absorber ma for example be a nanoparticle such as a gold
nanoparticles, a dye, etc.
[0051] In examples of implementation described below, results were
obtained for experiments illustrating the potential of tailoring of
laser pulses to control microcavitation for surgical applications
relying on the creation of selective alterations in tissues
containing pigments that strongly absorb laser light. For such
applications and the like, there may be provided a method for the
treatment of a disease or a condition necessitating selectively
destroying an affected tissue or organ having a liquid phase of a
subject in need thereof, comprising the step of irradiating said
tissue or organ with laser pulses produced by the laser system of
an embodiment of the invention. More particularly, the disease or
condition may be such as: kidney stones, bezoars or gallstones,
cancer or an ophthalmologic condition, such as, for example:
floaters (such as opacities, vitreous strands, etc.), retinal
disease, glaucoma; ametropia or cataracts.
[0052] Alternatively, the present method may be carried out for
laser tissue ablation or microsurgery. Particularly, surgical
procedures that require precise damage confinement may use
implementations of the method and/or system described herein.
Examples of such procedures include amongst others: lithotripsy or
surgical procedures such as tumor destruction or selective laser
trabeculoplasty, retinal surgery in general such as refractive
surgery or laser vitreolysis, capsulotomy or. More particularly,
the method is carried out in a subject in need thereof, i.e. that
is suffering from the particular medical condition. Most
particularly, the subject is a mammal, preferably a human
subject.
[0053] Alternatively, the method is used for selective
photothermolysis, such as, for example, for tattoo or hair
removal.
[0054] For such applications, one motivation is to confine the
alterations within a limited, predictable volume of tissue around
the absorbers, in order to spare adjacent tissues not being
targeted by the treatment. For example, in selective retina therapy
(SRT), the absorption of laser light by melanin pigments
synthetized in the melanosomes, which are membrane-bound organelles
of the retinal pigment epithelium (RPE) cells, can be exploited to
selectively alter these cells by laser-directed microcavitation. As
the rationale of SRT is to alter RPE cells while sparing adjacent
retinal tissue layers, including the photoreceptors, it is desired
to confine tissue alterations within a volume that does not include
these adjacent layers. It will be readily understood, however, that
the teachings of the present description are not limited to SRT
applications. Medical applications including lithotripsy, cell
destruction in cancer research or the treatment of other conditions
such as glaucoma are other examples of possible embodiments. In
some implementations, the medium may be an in vitro medium.
[0055] Additionally, the present method may be used for detecting
the presence of a foreign/abnormal body that is light absorbing in
a medium having a liquid phase, whereby the generation of
detectable microcavitation bubbles in the medium is indicative of
the presence of the foreign body. Diagnostic applications can thus
be envisioned, for example for the detection of malaria
(Lukianova-Hleb et al., "Hemozoin-generated vapor nanobubbles for
transdermal reagent-and needle-free detection of malaria" PNAS 2014
111 (3) 900-905; published ahead of print Dec. 30, 2013,
doi:10.1073/pnas.1316253111). As is known in the art, malaria
parasites digest hemoglobin to for intraparasite particles referred
to as "hemozoin". Hemozoin strongly absorbs energy from laser
pulses, which is diffused in the surrounding liquid. This leads to
the generation of nanobubbles around the hemozoin. As hemozoin
particles are much stronger light absorbers than hemoglobin, the
presence of the bubbles is indicative of the presence of malaria
parasites in the blood. The bubbles can be detected through known
techniques such as optical scattering imaging or photoacoustic
methods.
[0056] In other implementations, controlled microcavitation may be
used in conjunction with non-biological media, inasmuch as it
involves a medium has a liquid phase. Embodiments may therefore
provide a method for processing a material using microcavitation,
the material comprising a medium having a liquid phase or being in
contact with a medium having a liquid phase. The method involves
the step of irradiating the medium with laser pulses produced by a
laser system according to an embodiment of the invention.
[0057] As one skilled in the art will readily understand, the
reference to a medium having a liquid phase does not necessarily
imply that the medium exists in liquid form prior to the bubble
generation process. Indeed, in some embodiments the medium may be
in solid form and heated, using the laser system dedicated to
microcavitation or another heating mechanism, to fuse the medium
into its liquid phase so that microbubbles may be formed therein.
In other embodiments, the material being processed may not itself
define the medium having a liquid phase, but may be put in contact
with such a medium, for example water or the like. In such a case,
microcavitation bubbles may be generated in the neighboring medium
and their proximity to the material can be used to affect this
material in a desired fashion.
[0058] Of course, it will be readily understood that methods and
systems according to embodiments may be used in the context of
other applications than those described above without departing
from the scope of the present invention.
Method for the Controlled Generation of Microcavitation Bubbles
[0059] In accordance with various implementations, there is
provided a method for the controlled generation of microcavitation
bubbles in a medium having a liquid phase.
[0060] The method involves generating one or more laser pulses. One
skilled in the art will readily understand that laser pulses may be
generated by a number of devices or combination of devices, as
explained further below. The plurality of laser pulses may define a
pulse train emitted at a given repetition rate which can be
selected in view of the various operating parameters of the method
as known to those skilled in the art. The duration of each laser
pulse may be defined as the time interval between the onset of the
pulse and its end. Typically the pulse duration can be of the order
of 1 ns to 5000 ns, as dictated by the physical factors at play in
a given implementation. In accordance with one aspect, each laser
pulse is characterized by a time-dependent pulse parameter which is
controllable over the pulse duration, as explained below.
[0061] The method further involves irradiating the medium with
laser pulses having a radiant exposure sufficient to initiate
microcavitation within the medium during exposure to each laser
pulse.
[0062] The expression "radiant exposure", (symbol "H"), is
understood to refer to the laser energy impinging on the medium per
unit area, and can for example be expressed in units of
my/cm.sup.2. As one skilled in the art will readily understand, the
radiant exposure during a laser pulse is determined by both the
power distribution and the spatial distribution of light within the
laser pulse as a function of time. For any given implementation, a
desired radiant exposure can be obtained through a proper control
of the laser pulse generation conditions, as well as through the
provision of one or more optical component in a path of the laser
pulse which act to focus, collimate, redirect, amplify, modulate or
otherwise affect the properties of the laser pulses.
[0063] Radiant exposure can be considered sufficient to initiate
microcavitation within the medium during any given laser pulse if
it is greater than a minimum value at which the onset of
microbubble generation is observed, this minimum value being
typically referred to as the "threshold radiant exposure", denoted
as "H.sub.T".
[0064] The method further involves controlling a time-dependent
pulse parameter of each laser pulse. This control will be better
understood when described with respect to exemplary embodiments in
the section below, using the amplitude of the laser pulses as the
time-dependent pulse parameter.
Tailoring of the Amplitude Profile of the Laser Pulses
[0065] In some implementations, the time-dependent pulse parameter
is embodied by the amplitude of the laser pulses. As will be
readily understood by one skilled in the art, the amplitude of
light refers to the instantaneous fluxes of photons impinging on
the medium, for example can be expressed in terms of instantaneous
power (W) or directly in photons/s. The variation of the amplitude
of a laser pulse over the duration of the pulse is often referred
to in the art as the amplitude profile of the pulse or simply the
"pulse shape".
[0066] In examples of implementations, both the threshold radiant
exposure H.sub.T and the cavitation dynamics were found to be
strongly dependent on the pulse shape. "Cavitation dynamics" is
understood to refer in general to the evolution of the bubble
characteristics, including its size, during its formation, growth
and collapse phases. This dynamics depends on the details of the
vaporization kinetics of the medium under time-dependent absorption
of laser energy. Differences of up to 40% in the value of the
threshold radiant exposure were noticed when using pulses of the
same duration but having different pulse shapes. The pulse shape
can also have a major impact on the maximum bubble volume at
suprathreshold radiant exposures (above H.sub.T).
[0067] In accordance with one aspect, the pulse shape or another
time-dependent parameter is controlled according to a generally
positive variation over the pulse duration, such that the medium
absorbs more energy from the laser pulse at an end of the pulse
duration than at a beginning thereof.
[0068] Referring to FIG. 4, there is shown one example of a laser
pulse having a sawtooth-like shape with a positive slope, and which
defines what is generally referred to as "generally positive
variation". Such a pulse shape differs strongly from the shape of
pulses typically used for generating microcavitation bubbles.
Typically, Q-switched lasers are used for laser-induced
microcavitation, as such lasers emit pulses of the required
energies using a mature and well known pulse-generating scheme.
Q-switch lasers typically produce pulse shapes characterized by a
steep rise time followed by a long tail, such as shown in FIG. 3
(PRIOR ART). Such a pulse shape can therefore be said to have a
generally negative variation, and a medium exposed to such a pulse
shape would absorb a greater quantity of energy from the laser
pulse at the beginning of the pulse duration than at its end, in
direct contrast with laser pulses used in embodiments described
herein.
[0069] It will be readily understood that the reference to a
generally positive variation should be understood to a profile
which on average defines a positive slope, but that the variation
need not be positive over the entire duration of the pulses. In
some embodiments, the profile of the pulse amplitude or other
parameter may include plateaus, peaks, valleys and or other
irregular features without departing from the scope of the
invention.
[0070] With additional reference to FIGS. 5 and 6, experimental
results of microcavitation bubble generation using the pulse shape
of FIG. 4 are shown and compared to results obtained in similar
conditions but using the typical Q-switch-like shape of FIG. 3.
Melanin from Sepia officinalis and bovine melanosomes suspended in
water were used as models in these experiments. Using a pump-probe
setup and time-resolved imaging, the threshold radiant exposure
H.sub.T for the onset of microcavitation was measured upon
single-pulse irradiation at a wavelength of 532 nm with different
laser pulse formats having durations in the range of 2 ns to 630
ns. The cavitation dynamics and the bubble lifetime were also
characterized as a function of the radiant exposure above H.sub.T.
A pulse-programmable, frequency-doubled pulsed fiber laser was
employed to produce the different pulse formats. Details about the
pulse shaping capabilities of this laser platform can be found
elsewhere (P. Deladurantaye et al., Ultra Stable, Industrial Green
Tailored Pulse Fiber Laser with Diffraction-limited Beam Quality
for Advanced Micromachining, 2011 J. Phys.: Conf. Ser. 276
012017).
[0071] FIG. 5 compares the average maximum cavitation bubble volume
measured for laser pulses having the sawtooth shape of FIG. 4 and
for Q-switch-like laser pulses such as shown in FIG. 3 for
different radiant exposures. All pulses in both formats had the
same duration (630 ns) and the same wavelength (532 nm). The
average maximum bubble volume is illustrated as a function of the
radiant exposure H normalized to the threshold radiant exposure
H.sub.T.
[0072] In the experiment reported at FIG. 5, threshold radiant
exposures of (212+21/-16) mJ/cm.sup.2 and (148+16/-9) mJ/cm.sup.2
were measured for the pulse shape of FIG. 3 and that of FIG. 4,
respectively, and it can be observed that sawtooth-like pulses
yield a threshold radiant exposure about 40% lower than Q-switch
like pulses. Furthermore, the sawtooth-like shape produced bubbles
having a nearly constant maximum volume over an appreciable range
of radiant exposures (more than twice H.sub.T), whereas for the
Q-switch like shape the bubble volume increased sharply above 1.4
H.sub.T. Close to 2 H.sub.T, the Q-switch-like shape produced
bubbles having an average volume about ten times larger than the
volume of the bubbles generated with the sawtooth-like shape.
[0073] FIG. 6 presents details of the cavitation dynamics observed
in the same experiment as for the results of FIG. 5. As can be
observed, the Q-switch like shape produced two types of responses:
one characterized by bubbles whose lifetime scaled with radiant
exposure (column (a)) and the other by multiple short-lived bubbles
with lifetimes nearly independent of radiant exposure (column (b)).
The behavior depicted in column (a) was observed for the vast
majority (about 80%) of measurements carried out with the Q-switch
like shape for radiant exposures between 1.5 H.sub.T and 1.87
H.sub.T. Consequently, the potential of bubble size control through
self-limitation as described by Neumann and Brinkmann (cite above)
appears limited for a Q-switch-like pulse format such as the one
shown in FIG. 3. With the sawtooth-like shape of FIG. 4, only
relatively short-lived bubbles with lifetimes nearly independent of
radiant exposure where observed (column (c)). It is of interest to
mention that the threshold radiant exposure obtained with the
sawtooth-like shape (148 mJ/cm.sup.2) is 4.2 times lower than the
threshold reported by Neumann and Brinkmann (620 mJ/cm.sup.2) for a
pulse duration of 1.8 .mu.s, with still no increase of the bubble
volume above H.sub.T despite the shorter pulse duration.
[0074] Taken together, the results reported in FIGS. 5 and 6
demonstrate that pulse tailoring, here embodied by a sawtooth-like
shape, allows for optimizing both thermal and photomechanical
confinements.
[0075] The lower threshold radiant exposure obtained using laser
pulses having the sawtooth-like shape instead of the Q-switch-like
shape can be at least partially understood using relatively simple
physical arguments. At threshold, microcavitation is initiated near
the end of the laser pulse, as the threshold corresponds to the
condition for which all of the pulse energy is required to cause
vaporization of the medium. Since for the Q-switch-like shape more
energy is provided at the beginning of the pulse, more energy is
required to reach the critical nucleation temperature because heat
diffusion is more important during the rest of the pulse than for
the sawtooth-like shape. The quick energy coupling arising with the
Q-switch-like shape produces a steeper thermal gradient early in
the pulse. Due to this steeper temperature gradient, heat losses
are more important during the last part of the Q-switch-like pulse,
compared to the sawtooth-like shape. Because of these higher
thermal losses, more laser energy is required to reach the
nucleation temperature when using the Q-switch-like pulse.
[0076] As regards to the cavitation dynamics above threshold, the
situation is more complex and more aspects need to be considered to
understand the observed differences. Important aspects include the
formation of a thermally insulating vapor blanket around the
absorption centers and the volume of superheated, metastable media
(J. Neumann and R. Brinkmann, Self-limited growth of laser-induced
vapor bubbles around single microabsorbers, Applied Physics
Letters; Vol. 93, Issue 3, Jul. 21, 2008). The latter determines
the amount of energy stored in the medium that can be converted
into kinetic energy of the bubble during its expansion. An
interpretation based on qualitative arguments is proposed for the
results discussed above. The increase of the radiant exposure above
the threshold with pulses of Q-switch like format gives rise to
steeper and steeper temperature gradients at the beginning of the
pulse, which, in turn, results in increasingly important heat
fluxes that can be converted into bubble energy. Indeed, because
more heat losses occur when delivering more energy at the beginning
of the pulse than at the end, the thermal boundary layer thickness
is larger with Q-switch-like pulse formats compared to
sawtooth-like formats. Consequently, more energy is available from
the medium to drive bubble expansion when Q-switch-like pulse
formats are employed, and larger bubbles are produced. One aspect
of pulse tailoring-based control of microcavitation is therefore
linked with the choice of shapes that minimize heat losses, since
heat losses directly determine the volume of medium that is
thermally affected, while also driving bubble growth.
[0077] Furthermore, with the sawtooth-like shape, it can be
suggested that cavitation bubbles are shielding laser energy
absorption for the most intense part of the pulse, whereas for the
Q-switch like shape this most intense part is not shielded for a
broad range of radiant exposures above threshold. The shielding
effect provided by bubble growth prevents useless absorption of
energy from the part of the pulse that follows bubble incipience.
With the Q-switch like format, the medium is irradiated upfront
with the most powerful part of the pulse, yielding larger bubbles
for the reasons exposed above. On the other hand, for the
sawtooth-like format the shielding effect "shuts down" intense,
useless parts of the pulse that could otherwise produce larger
temperature gradients and drive growth of larger bubbles.
[0078] Another possible origin of the more explosive bubble
behaviors observed with the Q-switch-like may be linked with the
evolution of the bubble incipience time .tau..sub.inc at
suprathreshold radiant exposures. As the radiant exposure is
increased above threshold, the higher heating rates allow the
nucleation temperature to be reached earlier, in other words
.tau..sub.inc decreases with increasing radiant exposure. As such,
.tau..sub.inc can be seen as an effective initial heating time or
effective pulse duration for a given radiant exposure, since the
expanding bubble can thermally insulate the melanosome and to some
extent shield further absorption of laser energy at later times.
The inventors have experimentally and theoretically shown that
.tau..sub.inc is shorter for the Q-switch format than for the
sawtooth format, at a given radiant exposure. As pointed out by
Neumann and Brinkmann, shorter durations lead to more explosive
vaporizations. Therefore, the larger bubble volumes produced by
Q-switch-like formats would be associated with a shorter effective
heating time or pulse duration at a given suprathreshold radiant
exposure.
[0079] From the discussion above, it will be readily understood
that the benefits of pulse tailoring for the control of
microcavitation are not limited to sawtooth-like pulse shapes. In
alternative embodiments, similar advantages may be obtained from a
variety of laser pulse amplitude profiles. As will be readily
understood by one skilled in the art, this may for example be
achieved by choosing a profile that promotes a higher average
energy absorption by the medium during a second phase of the pulse
than during a preceding first phase, as is the case with the
sawtooth shape with a positive slope. Indeed a variety of pulse
shapes having a generally positive variation over the pulse
duration can provide the shielding effect described above, if it is
such that the medium absorbs a greater quantity of energy from the
laser pulse at an end of the pulse duration than at the beginning
thereof. The pulse shape may for example be said to define a
crescendo, or having a greater amplitude at a later moment in time
than it does at the onset of the pulse.
[0080] Other, non-limitative examples of laser pulse shapes that
may be of interest are shown in FIG. 7. From top to bottom, the
first three pulse shapes are shown to include a first phase of
regularly increasing amplitude, followed by a second phase of
sharply decreasing amplitude. In the next two examples, the
illustrated pulse shapes include an initial phase defining a low
step, followed by a sharp increasing amplitude phase and a
sharply-decreasing amplitude phase, sequentially, with an optional
plateau therebetween. Finally, in the bottommost illustrated
example the pulse shape is shown to include a sequence of
triangular sub-pulses of gradually increasing peak amplitude.
[0081] Referring to FIG. 8, there is shown another embodiment where
the laser pulse shape is defined by a sequence of n sub-pulses of
gradually increasing peak amplitude. In such an implementation, in
addition to the time-dependent pulse parameter such as the pulse
shape or spectrum, the time delays separating individual sub-pulses
within the pulse can be used to control the microcavitation bubble
generation process. As illustrated, at threshold, that is, if the
set of n sub-pulses collectively provides a radiant exposure equal
to or exceeding the threshold radiant exposure, cavitation starts
on sub-pulse n (line a). Upon increasing the energy of the laser
pulses, and therefore increasing the radiant exposure, the maximum
size of this bubble increases as shown in line b. Cavitation
however still starts during exposure to the n.sup.th sub-pulse. If
the radiant exposure is increased further, at some point enough
energy is available from the preceding (n-1) sub-pulse to initiate
microcavitation, leading to a "hopping" effect (line c). This jump
causes a reset of the maximum bubble size. This hopping process
repeats itself as the radiant exposure is further increased (lines
d-e), with the cavitation now starting on pulse n-2, then n-3 and
so on. At higher radiant exposures, multiple bubbles can be
generated and the hopping effect can combine with shielding
effects. Indeed, because bubbles can scatter and/or diffract light,
they can shield absorption centers from laser light during their
lifetime. In this example, this happens for radiant exposures such
that the lifetime of the bubble initiated at a given sub-pulse is
of the same order or larger than the delay between this sub-pulse
and the subsequent one. The lifetime of the created bubbles can
therefore be controlled so that it will not exceed a maximum value
through a proper determination of the sub-pulse characteristics and
the time delay between them.
Tailoring of Other Time-Dependent Parameters
[0082] In the examples given above, the amplitude profile of the
light pulses was tailored as a function of time to obtain the
desired pulse shape. Other time-dependent pulse parameters may
however be tailored to achieve similar results. For example, in
other embodiments, the time-dependent pulse parameter may be
embodied by the spectral content of the laser pulse. As the
absorption of a medium generally varies with the laser wavelength,
spectral tailoring of the laser pulses can indeed be exploited to
tune the rate of energy absorption with the purpose of controlling
microcavitation. Such implementations may therefore include
tailoring the spectral profile of the laser pulses as a function of
time according to a generally positive variation, that is, using
wavelengths at the end of the pulse duration which are more
strongly absorbed by the medium than wavelengths at the beginning
of the laser pulses. In other embodiments, the time-dependent pulse
parameter may be embodied by the spatial profile of the laser
pulse. For example, changes of the beam shape during the pulse
duration can be employed to dynamically adjust the irradiance
incident within a given volume of medium with the purpose of
controlling microcavitation through precise tuning of the rate of
laser energy absorption in that volume.
Laser Systems
[0083] In accordance with another aspect, there is also provided a
laser system for generating microcavitation bubbles in a medium
having a liquid phase in a controlled manner.
[0084] Referring to FIG. 9, there is shown one example of a laser
system 50 according to one embodiment.
[0085] The laser system 50 includes a laser pulse generating
assembly 52 for generating a plurality of laser pulses 54. As
explained above, each laser pulse has a duration and a
time-dependent pulse parameter controllable over the pulse
duration. In the illustrated embodiment, control of the amplitude
of the laser pulses is provided, and the time-dependent pulse
parameter may therefore be embodied by the amplitude profile or
pulse shape of the laser pulses 54.
[0086] The laser pulses 54 have a radiant exposure sufficient to
initiate microcavitation within the medium 56 during each laser
pulse 54 when impinging on this medium. The radiant exposure may be
controlled through an adjustment of the optical power and spatial
distribution of the laser pulses, for example through a control of
their generation parameters and/or through additional optical
components.
[0087] In one example, the laser pulses 54 outputted by the laser
pulse generating assembly 52 may be carried by an optical fiber 58
toward the medium 56. It will be readily understood that any number
of optical components guiding, redirecting, focussing or otherwise
affecting the laser pulses may be provided between the output of
the laser pulse generating assembly 52 and the medium 56.
Furthermore, the laser system 50 may be integrated in a larger
apparatus or installation including any number of additional
components including electronic, digital, communications,
mechanical, optical components and the like without departing from
the scope of the invention.
[0088] In the illustrated example, the laser pulse generating
assembly 52 is based on a Master Oscillator, Power Amplifier (MOPA)
architecture. The laser pulse generating assembly 52 therefore
includes a seed light source 64, acting as a master oscillator, and
at least one optical power amplifier, first and second amplifiers
62a, 62b being shown in the example of FIG. 9. Still in this
example, the seed light source 64 operates preferably in a
continuous wave (CW) regime to generate a continuous light beam 65.
The seed light source 64 may for example be a laser diode, but any
other light source generating an appropriate CW beam could be
considered, such as for example a filtered ASE (Amplified
spontaneous emission) source, a superfluorescent source, a CW fiber
laser or a fiber coupled CW bulk solid-state laser source. The
continuous light beam 65 preferably has a spectral shape which will
determine the spectral shape of the laser pulses 54 outputted by
the laser pulse generating assembly 52. Advantageously, the seed
light source may be selected or replaced depending on the required
spectral profile of the outputted light. Alternatively, a
wavelength-tunable laser diode may be used. Additional components
may optionally be provided downstream the laser diode to modify its
spectral shape. An optical isolator may also be provided downstream
the seed laser diode to prevent feedback noise from reaching
it.
[0089] The first and second amplifiers 62a and 62b are provided in
series in the path of the light beam generated by the seed light
source. An appropriate optical pump signal from optical pump source
P1, propagating either backward or forward through the gain medium
of the first amplifier 62a, maintains the required population
inversion therein. Similarly, the second amplifier 62b may be
forward or backward pumped by a suitable optical pump source P2.
Both the first and the second amplifiers 62a and 62b may for
example be embodied by a length of polarization-maintaining
aluminosilicate optical fiber doped with rare earth elements such
as Erbium, Ytterbium, Holmium, Praseodymium, Neodymium or Thulium.
In yet other embodiments, additional optical components are
employed for optimizing the pulsed laser source stability, such as
optical isolators, polarizers, filters, etc. In a specific
embodiment, the first and second amplifiers 62a and 62b may include
a Semiconductor Optical Amplifier (SOA). Although FIG. 9 shows two
amplifications stages in the laser pulse generating assembly,
different numbers of amplifiers may be used in other
implementations. In some embodiments, an amplifier chain comprising
several cascaded amplifier stages is used for the final pulse
amplification. In a particular embodiment, the amplifier chain may
include at least one DPSS (diode-pumped solid state) amplifier
stage based on gain medium like Nd:YAG or Nd:YVO.sub.4. Those
skilled in the art will recognize numerous variations and
alternatives.
[0090] Still referring to FIG. 9, in the illustrated embodiment the
laser pulse generating assembly 52 further includes a first optical
amplitude modulator 66 temporally modulating the continuous light
beam 65, and thereby converting it into laser pulses 54. The first
amplitude modulator 66 may for example be embodied by a Lithium
Niobate Mach-Zehnder electro-optic modulator suitable for
generating optical pulses with controlled features at the
nanosecond scale. In other embodiments, other modulation schemes,
such as based on an acousto-optic modulator, an electroabsorption
modulator, etc. could also be considered. The optical input port of
the first modulator 66 is coupled to the seed light source 64 to
receive the continuous light beam 65 therefrom. Preferably, the
whole laser pulse generating assembly 52 is an all-fiber device,
but it will be understood by one skilled in the art that additional
optical components such as mirrors, lenses, spectral shaping
elements or any other appropriate element may be provided between
the CW light source 64 and the first modulator 66 without departing
from the scope of the present invention.
[0091] The laser pulse generating assembly 52 may also include a
second optical amplitude modulator 68, interposed between the two
amplifiers 62a and 62b. According to some embodiments, the final
shape of the laser pulses 54 outputted by the laser pulse
generating assembly 54 will be determined by the combined action of
both modulators 66 and 68.
[0092] The laser system 50 further includes a pulse-shaping
mechanism. The pulse shaping mechanism is configured to control the
time-dependent pulse parameter of each laser pulse 54 according to
a generally positive variation over the pulse duration, such that
the medium 56 absorbs a greater quantity of energy from the laser
pulse 54 at an end of the pulse duration than at its beginning. As
explained above, the time-dependent pulse parameter may be the
amplitude, the spectral content or the spatial shape of the laser
pulses. Suitable shapes having a generally positive variation can
be for example a sawtooth shape, another one of the shapes
illustrated in FIG. 7 or other similar shapes allowing the
optimizing of thermal and photomechanical confinements, as also
explained above.
[0093] It will be readily understood that the pulse shaping
mechanism may be embodied by any device or combination of devices
apt to control the laser pulse generating assembly in order to
produce the desired pulse shape. In the illustrated embodiment of
FIG. 9, the pulse shaping mechanism is embodied by a digital pulse
shaping module 60. The digital pulse shaping module 60 provides
control signals to components of the laser pulse generating
assembly 52 in order to control the pulse shape of the laser pulses
54. In the illustrated embodiment, the control signal are embodied
by a SHAPE signal and a GATE signal respectively controlling the
opening and closing of the first and second amplitude modulators 66
and 68. The first and second modulators 66 and 68 may be partially
or fully synchronized with each other, depending on the shape
desired for the resulting laser pulses. The term "synchronized" is
used herein as describing the joint timing of the opening and
closing of the first and second modulators 66 and 68, taking into
account the transit time of the light between both modulators. For
example, the two modulators 66 and 68 will be considered fully
synchronized if the second modulator 68 opens exactly at the
instant the leading edge of the pulse generated by the first
modulator 66 reaches it, and closes at the instant this pulse ends.
Synchronization of the two modulators 66 and 68 may be used
advantageously to control the pulse shape of the laser pulses. For
example, by setting the two modulators 66 and 68 partially out of
synchronization, pulses of a very small width may be obtained.
Combining drive pulses of different durations and shapes may also
advantageously be used to tailor the resulting light pulses to a
wide range of specifications and with a very high time
resolution.
[0094] The digital pulse shaping module 60 may be embodied by
various configurations apt to provide control signals of the
desired shape and resolution. One such platform is for example
described in U.S. Pat. No. 8,073,027 (DELADURANTAYE et al.), the
contents of which being incorporated herein by reference. It is
however understood that in other embodiments pulse shaping control
may be performed using different components which may be digital or
analog without departing from the scope of the invention.
[0095] In some implementations, when it is desired to work with
laser pulses at a wavelength which is a harmonic of the fundamental
laser wavelength, the laser pulse generating assembly may further
include one or more frequency conversion modules 70, for example
following the second optical amplifier or optical amplifier chain.
As the frequency conversion is non-linear, the pulse shaping
capacity of the digital pulse shaping module may compensate the
nonlinearity so as to generate precisely the desired optical pulse
shape at the harmonics wavelengths.
[0096] Referring to FIG. 10, there is shown another example of a
laser system 50 for generating microcavitation bubbles, according
to one implementation.
[0097] The illustrated laser system 50 of FIG. 10 again has a
Master Oscillator Power Amplifier (MOPA) architecture. In this
embodiment, the laser pulse generating assembly 52 includes a seed
light source 64 generating the laser pulses 54. A series of optical
fiber amplifiers 62a, . . . 62n are provided downstream the laser
pulse generating assembly 52 to provide light amplification.
[0098] The seed light source 64 may be embodied by a semiconductor
laser diode of any appropriate configuration such as a Fabry-Perot
cavity, a distributed-feedback diode, an external-cavity diode
laser (ECDL), etc. A pulse generator 71 electrically drives the
seed light source 64 to control the pulse characteristics. In some
embodiments, the pulse generator 71 may define the pulse shaping
mechanism configured to control the time-dependent pulse parameter
of the laser pulses according to a generally positive variation
over the pulse duration, as explained above. In some variants, the
pulse shaping mechanism may further include a spectrum tailoring
module 72, as for example illustrated in FIG. 10. The spectrum
tailoring module can tailor the spectral profile of the laser
pulses 54 generated by the laser pulse generating assembly 52. In
the illustrated embodiment, the spectrum tailoring module 72
includes a phase modulator 74 which imposes a time-dependent phase
variation on each laser pulse 54 therethrough. Preferably, a phase
modulator driver 76 drives the activation of the phase modulator 74
through a phase variation drive signal 78 providing the desired
phase variation. The phase modulator 74 may be embodied by an
electro-optic component based modulator such as well-known in the
art. The electro-optical material included in the phase modulator
can be LiNbO.sub.3, LiTaO.sub.3, KNbO.sub.3 or any other
appropriate nonlinear material. Alternatively, the phase modulator
may be based on an acousto-optical component such as an
acousto-optic modulator.
[0099] Advantageously, the spectral tailoring module may be used to
control the spectral content of the laser pulses according to the
principles explained above. Furthermore, spectral tailoring may
alternatively or additionally provide mitigation of non-linear
effects for high power pulses. More details on spectral tailoring
may for example be described in U.S. Pat. No. 7,974,319
(DELADURANTAYE et al.), the contents of which is incorporated
herein by reference.
[0100] It will be readily understood that the embodiments shown in
FIGS. 9 and 10 are just some of a number of possible
implementations of a laser system according to an aspect of the
invention. For example, in some variants the seed light source may
be a pulses laser source, directly modulated by control signals
from the pulse shaping mechanism to generate the laser pulses.
Pulsed seed laser sources may be combined with external optical
modulators for additional pulse shaping. In other implementations,
the pulse shaping mechanism may provide a control the spatial
profile as the time-dependent parameter of the laser pulses.
Spatial tailoring may be accomplished by systems such as described
in U.S. Pat. No. 8,254,015 (TAILLON et al.), the contents of which
being incorporated herein by reference. Other laser systems
suitable for use in the context of the present method include, for
example, model PPL 400 laser from PicoQuant, Spectra-Physics'
Quasar laser and laser model PyroFlex 25 from Electro-Scientific
Industries.
[0101] Of course, numerous modifications could be made to the
embodiment above without departing from the scope of the present
invention.
* * * * *