U.S. patent application number 11/771361 was filed with the patent office on 2008-10-16 for nanoparticle treated medical devices.
This patent application is currently assigned to Ethicon Endo-Surgery, Inc.. Invention is credited to Daniel F. Dlugos, Robert P. Gill, Michael A. Murray, Carl I. Shurtleff, James W. Voegele.
Application Number | 20080255425 11/771361 |
Document ID | / |
Family ID | 39854351 |
Filed Date | 2008-10-16 |
United States Patent
Application |
20080255425 |
Kind Code |
A1 |
Voegele; James W. ; et
al. |
October 16, 2008 |
NANOPARTICLE TREATED MEDICAL DEVICES
Abstract
Various compositions, methods, and devices are provided that use
fluorescent nanoparticles, which can function as markers,
indicators, and light sources. The fluorescent nanoparticles can be
formed from a fluorophore core surrounded by a biocompatible shell,
such as a silica shell. In one embodiment, the fluorescent
nanoparticles can be delivered to tissue to mark the tissue, enable
identification and location of the tissue, and/or illuminate an
area surrounding the tissue. In another embodiment, the fluorescent
nanoparticles can be used on a device or implant to locate the
device or implant in the body, indicate an orientation of the
device or implant, and/or illuminate an area surrounding the device
or implant. The fluorescent nanoparticles can also be used to
provide a therapeutic effect.
Inventors: |
Voegele; James W.;
(Cincinnati, OH) ; Gill; Robert P.; (Mason,
OH) ; Murray; Michael A.; (Bellevue, KY) ;
Dlugos; Daniel F.; (Middletown, OH) ; Shurtleff; Carl
I.; (Mason, OH) |
Correspondence
Address: |
NUTTER MCCLENNEN & FISH LLP
WORLD TRADE CENTER WEST, 155 SEAPORT BOULEVARD
BOSTON
MA
02210-2604
US
|
Assignee: |
Ethicon Endo-Surgery, Inc.
Cincinati
OH
|
Family ID: |
39854351 |
Appl. No.: |
11/771361 |
Filed: |
June 29, 2007 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
60911546 |
Apr 13, 2007 |
|
|
|
Current U.S.
Class: |
600/160 ; 606/1;
606/230; 623/23.75 |
Current CPC
Class: |
A61B 5/415 20130101;
A61B 5/0075 20130101; A61B 5/0084 20130101; A61B 5/418 20130101;
A61K 49/0017 20130101; A61B 5/0071 20130101; A61B 1/043 20130101;
A61K 41/0052 20130101; A61B 1/3132 20130101; A61K 49/0093
20130101 |
Class at
Publication: |
600/160 ; 606/1;
606/230; 623/23.75 |
International
Class: |
A61B 1/00 20060101
A61B001/00; A61B 17/00 20060101 A61B017/00; A61B 17/04 20060101
A61B017/04; A61F 2/00 20060101 A61F002/00 |
Claims
1. A medical device, comprising: a biocompatible body adapted to be
at least partially disposed within a patient's body, the body
having at least one fluorescent nanoparticle adapted to fluoresce
when energy is delivered thereto.
2. The device of claim 1, wherein the at least one fluorescent
nanoparticle is adapted to illuminate an area surrounding the body
when energy is delivered thereto.
3. The device of claim 1, wherein the at least one fluorescent
nanoparticle is adapted to indicate an orientation of the body when
energy is delivered thereto.
4. The device of claim 1, wherein the at least one fluorescent
nanoparticle is embedded in the body.
5. The device of claim 1, wherein the at least one fluorescent
nanoparticle is coated on the body.
6. The device of claim 1, wherein the at least one fluorescent
nanoparticle is disposed within a cavity formed in the body.
7. The medical device of claim 1, wherein the body comprises an
elongate shaft having a proximal end adapted to remain outside of a
patient's body and a distal end adapted to be disposed within a
patient's body.
8. The medical device of claim 7, wherein the at least one
fluorescent nanoparticle is located on the distal end of the
elongate shaft.
9. The medical device of claim 1, wherein the biocompatible body
comprises an implant containing the at least one fluorescent
nanoparticle.
10. The medical device of claim 1, wherein the biocompatible body
comprises a suture.
11. The medical device of claim 1, wherein the biocompatible body
is absorbable.
12. The device of claim 7, wherein the elongate shaft includes an
inner lumen extending therethrough and defining a working
channel.
13. A medical device, comprising: an elongate shaft having a
proximal end adapted to remain outside of a patient's body and a
distal end adapted to be disposed within a patient's body; and at
least one fluorescent nanoparticle associated with the elongate
shaft and adapted to fluoresce when energy is delivered
thereto.
14. The device of claim 13, wherein the at least one fluorescent
nanoparticle is adapted to illuminate an area surrounding the
elongate shaft when energy is delivered thereto.
15. The device of claim 13, wherein the at least one fluorescent
nanoparticle is adapted to indicate an orientation of the elongate
shaft when energy is delivered thereto.
16. A surgical method, comprising: positioning a device in a
patient's body, the device containing at least one fluorescent
nanoparticle; and delivering energy to the at least one fluorescent
nanoparticle to cause the at least one fluorescent nanoparticle to
fluoresce.
17. The method of claim 16, wherein the at least one nanoparticle
illuminates an area surrounding the device when energy is delivered
thereto.
18. The method of claim 16, further comprising viewing the at least
one fluorescent nanoparticle after energy is delivered thereto to
locate the device.
19. The method of claim 16, further comprising viewing the at least
one fluorescent nanoparticle after energy is delivered thereto to
determine an orientation of the device.
20. The method of claim 16, wherein the device comprises an
implant.
21. The method of claim 20, wherein, when energy is delivered to
the at least one fluorescent nanoparticle, the at least one
fluorescent nanoparticle indicates a location of a port on the
implant.
22. The method of claim 20, wherein, when energy is delivered to
the at least one fluorescent nanoparticle, the at least one
fluorescent nanoparticle indicates a size of the implant.
23. The method of claim 16, wherein the device comprises an
elongate shaft having a distal end positioned in a body lumen of
the patient while a proximal end of the elongate shaft remains
external to the patient.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to U.S. Provisional Patent
Application No. 60/911,546 filed on Apr. 13, 2007 and entitled
"Fluorescent Nanoparticle Compositions, Methods, and Devices,"
which is hereby incorporated by reference in its entirety.
FIELD OF THE INVENTION
[0002] The present invention relates to fluorescent nanoparticles,
and in particular to various compositions, methods, and devices
that use fluorescent nanoparticles.
BACKGROUND OF THE INVENTION
[0003] Illuminating light incident on tissue is transmitted
through, scattered by, absorbed, or reflected by that tissue. At
certain wavelengths, after absorbing the illuminating light, tissue
can re-emit light energy at a different wavelength
(autofluorescence). If a substance is introduced into the tissue or
is present between tissue layers, or in lumens, it can fluoresce
after absorbing incident light as well. Detecting devices can be
placed in relationship to the tissue to image light that is
transmitted, scattered, reflected, or fluoresced from the tissue.
It is well known in the art that certain wavelengths of light tend
to be preferentially absorbed, reflected, or transmitted through
different types of tissue. Generally, near infrared light (600-1300
nm) tends to coincide with minima in the spectral absorption curve
of tissue, and thus allows the deepest penetration and transmission
of light. For optical analysis of surface structures or diagnosis
of diseases very close to the body surface or body cavity surfaces
or lumens, UV light and visible light below 600 nm can also be
used, as it tends to be absorbed or reflected near the surface of
the tissue.
[0004] Various modalities are currently used for imaging of tissue
and organs, including visible light endoscopes, ultrasound,
magnetic resonance imaging (MRI), computed tomography (CT), and
positron emission tomography (PET). Many anatomical spaces and
tissues, however, are not easily accessible and viewable. Moreover,
the use of imaging equipment can be expensive and time consuming,
and their application is often limited.
[0005] Various contrast agents are also employed to effect image
enhancement in a variety of fields of diagnostic imaging, the most
important of these being X-ray, magnetic resonance imaging (MRI),
ultrasound imaging, and nuclear medicine. Additionally, optical
labels, such as fluorescent dyes, are introduced into tissue
samples to signal abnormal biological and/or chemical conditions of
tissues of a living subject. Despite many successful applications,
conventional optical labels have many drawbacks. For example,
conventional optical labels are generally toxic to living cells and
tissues comprised of living cells. Additionally, conventional
optical labels such as fluorescent dyes generally suffer from
short-lived fluorescence because the dyes undergo photo bleaching
after minutes of exposure to an excitation light source. This
renders them unsuitable for optical imaging that requires extended
time period of monitoring. Moreover, conventional optical labels
are sensitive to environmental changes such as pH and oxygen
concentration. Another drawback of conventional optical labels is
that typically the excitation spectra of such labels are quite
narrow, while the emission spectra of such labels is relatively
broad, resulting in overlapping emission spectra. Thus, when a
combination of conventional optical labels with different emission
spectra are used in optical imaging, multiple filters are need to
detect the resultant emission spectra of the combination.
Additionally, fluorescent labels are generally inefficient at
converting the excitation light to the emission wavelength, and the
resulting signal can be very weak.
[0006] Accordingly, there remains a need for improved compositions,
methods, and devices for use in medical imagining, and more
particularly for marking, indicating, and illuminating tissue.
SUMMARY OF THE INVENTION
[0007] The present invention generally provides various
compositions, methods, and devices for using fluorescent
nanoparticles as markers, indicators, and/or light sources. In one
embodiment, an endoscopic adaptor for viewing fluorescent
nanoparticles is provided and includes first and second members
removably matable to one another, e.g., using threads or other
mating elements, and adapted to engage a portion of an endoscope
eyepiece therebetween. The first member can have a viewing lumen
formed therethrough and adapted to axially align with a viewing
lumen formed in an endoscope eyepiece, and a cavity formed therein
for seating a filter adapted to filter light received through the
viewing lumen of the first member. The device can also include a
filter disposed within the cavity in the first member. In an
exemplary embodiment, the filter is adapted to transmit light in
the fluorescent waveband. For example, the filter can be an
interferometric long-pass filter.
[0008] The components of the adaptor can have a variety of
configurations. In one embodiment, the second member can be in the
form of a ring having a lumen extending therethrough with an
enlarged diameter portion adapted to receive an enlarged diameter
portion formed on an endoscopic eyepiece. The second member can
also optionally include first and second hemi-cylindrical halves
that are hingedly mated to one another to allow the second member
to be positioned around an endoscopic eyepiece. In an another
embodiment, the device can include a filter cartridge removably
disposed within the first member and adapted to retain a filter
therein. For example, the first member can include a slot formed
therein and extending across the viewing lumen for receiving the
filter cartridge such that a filter containing in the filter
cartridge is disposed across the viewing lumen.
[0009] In yet another embodiment, an endoscopic system is provided
and includes an endoscope eyepiece having a viewing lumen formed
therethrough between proximal and distal ends thereof, and an
adaptor adapted to removably mate to the endoscope eyepiece and
adapted to retain a filter therein such that the filter is in
alignment with the viewing lumen formed in the endoscope eyepiece
to thereby filter light through the viewing lumen. The adaptor can
include a viewing lumen extending therethrough and adapted to be
aligned with the viewing lumen in the endoscope eyepiece when the
adaptor is mated to the endoscope eyepiece. In an exemplary
embodiment, the adaptor can be an eyepiece extension member having
the viewing lumen formed therein, and a mating element adapted to
mate to the eyepiece extension to engage a portion of the endoscope
eyepiece therebetween. A filter can optionally be removably or
fixedly disposed within the adaptor. In an exemplary embodiment,
the filter is adapted to transmit light in the fluorescent
waveband. In other aspects the adaptor can include a filter
cartridge removably disposed therein and adapted to retain a filter
therein.
[0010] Exemplary methods for viewing fluorescent nanoparticles are
also provided, and in one embodiment the method can include
coupling an adaptor to a proximal end of an endoscope, inserting a
distal end of the endoscope into a body lumen to position the
distal end in the direction of tissue containing at least one
fluorescent nanoparticle, and activating a light transmitting
element to emit fluorescent light onto the at least one fluorescent
nanoparticle such that reflected fluorescent light is transmitted
through a filter contained within the adaptor and is received by an
image obtaining element coupled to the endoscope. The light
transmitting element can extend through the endoscope to emit
fluorescent light onto the at least one fluorescent nanoparticle,
and the filter can be configured to block visible light.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] The invention will be more fully understood from the
following detailed description taken in conjunction with the
accompanying drawings, in which:
[0012] FIG. 1 is a side view of one embodiment of a fluorescent
nanoparticle having a core and a shell;
[0013] FIG. 2 is a perspective view of one embodiment of an
applicator for applying fluorescent nanoparticles to a tissue
surface;
[0014] FIG. 3A is a top view of a drug delivery pump having
fluorescent nanoparticles disposed around a bolus port for locating
the bolus port once the pump is implanted;
[0015] FIG. 3B is a side view of the drug delivery pump of FIG. 3A
implanted in tissue, showing a reading unit with a fluorescence
meter for identifying and locating the particles in the port and a
syringe about to be inserted through the port;
[0016] FIG. 4 is a perspective view of a gastric restriction band
having fluorescent nanoparticles disposed thereon for indicating a
size of the band;
[0017] FIG. 5A is a side view of an elongate shaft having
fluorescent nanoparticles disposed around a distal end thereof for
illuminating a body cavity;
[0018] FIG. 5B is a side view of an elongate shaft having
fluorescent nanoparticles disposed on a distal end thereof for
indicating an insertion depth of the elongate shaft into a body
lumen;
[0019] FIG. 5C is a side view of an elongate shaft having
fluorescent nanoparticles disposed to form an arrow indicating a
direction orientation of a distal end of the elongate shaft;
[0020] FIG. 6 is a diagram illustrating one embodiment of a
laparoscopic system for viewing fluorescent nanoparticles;
[0021] FIG. 7A is a diagram illustrating one embodiment of a
laparoscope having an image combiner for viewing visible and
non-visible wavelengths emitted by fluorescent nanoparticles;
[0022] FIG. 7B is a diagram illustrating the embodiment of FIG. 7A
incorporated into a hand held instrument with a self-contained
monitor or display output that feeds to other displays;
[0023] FIG. 8A is a cross-sectional view of one embodiment of an
adaptor mated to an endoscope eyepiece;
[0024] FIG. 8B is perspective view of one embodiment of mating
element for use with an adaptor configured to mate to an endoscope
eyepiece; and
[0025] FIG. 9 is a perspective view of another embodiment of a
portion of an adaptor for mating to an endoscope, showing a
removable filter cartridge.
DETAILED DESCRIPTION OF THE INVENTION
[0026] Certain exemplary embodiments will now be described to
provide an overall understanding of the principles of the
structure, function, manufacture, and use of the devices and
methods disclosed herein. One or more examples of these embodiments
are illustrated in the accompanying drawings. Those skilled in the
art will understand that the devices and methods specifically
described herein and illustrated in the accompanying drawings are
non-limiting exemplary embodiments and that the scope of the
present invention is defined solely by the claims. The features
illustrated or described in connection with one exemplary
embodiment may be combined with the features of other embodiments.
Such modifications and variations are intended to be included
within the scope of the present invention.
[0027] The present invention generally provides various
compositions, methods, and devices for using fluorescent
nanoparticles in various medical applications. In certain exemplary
embodiment, the fluorescent nanoparticles can be used to mark,
indicate, and/or illuminate an object, such as a device or tissue.
The particular configuration of the fluorescent nanoparticles can
vary, but preferably the nanoparticles are biocompatible and
non-toxic. The shape, size, and morphology of the nanoparticles can
vary. In an exemplary embodiment, as shown in FIG. 1, the
nanoparticles 10 can be formed from a fluorophore core 14 and a
biocompatible shell 12 that surrounds the core 14. The use of a
biocompatible shell is particularly advantageous as it is non-toxic
when used in medical applications. The shell can also be configured
to intensify the photophysical properties of the core such that,
when this dye is excited by light, the observed fluorescence is
brighter than the dye itself. This enables viewing through tissue
having a thickness of about 2 cm or less.
[0028] The particular materials used to form the core and the shell
can vary depending on the intended use, but in an exemplary
embodiment the core includes organic dye molecules and the shell is
silica-based. Fluorescing dyes are available at various
wavelengths, including both visible and non-visible wavelengths.
Dyes having any wavelength can be used with the present invention,
but the particular dye selected may depend on the intended use. For
example, where the dye needs to be viewed through tissue, the dye
preferably has a wavelength that is near or within the infrared
range, i.e., from about 600 nm to 1350 nm. Particular dyes in the
near infrared wavelength are preferred as they demonstrate the best
transmissibility for passing through tissue. In an exemplary
embodiment, the nanoparticles contain a dye that has an absorption
and emission cross-section in the region of about 800 nm. Exemplary
dyes are Cy 5.5 manufactured by GE Healthcare and Indocyanine Green
manufactured by Acros Organics N.V. In order to view dyes with an
emission cross-section outside of the visible spectrum for medical
applications, energy must be delivered to the dye to excite the
molecules and the resulting emission by the molecules must be
collected by specialized equipment sensitive to this non-visible
waveband. Various exemplary methods and devices for delivering
energy to dyes with emission cross-sections outside of the visible
spectrum will be discussed in more detail below. Where the dye does
not need to be viewed through tissue, or is viewed through very
thin tissue, the dye can have a wavelength that is within the
visible range, i.e., from about 400 nm to 700 nm. When used in the
body, light may need to be delivered to the tissue containing the
particles to enable viewing. The light source may be external to
the body for delivering light internally, or an internal light
source may be used for internal application.
[0029] A person skilled in the art will appreciate the fluorescent
nanoparticles can be formed from a variety of materials using
various methods. Exemplary fluorescent nanoparticles and methods
for making the same are disclosed in detail in U.S. Publication No.
2004/0101822 of Wiesner et al. entitled "Fluorescent Silica-Based
Nanoparticles," U.S. Publication No. 20046/0183246 of Wiesner et
al. entitled "Fluorescent Silica-Based Nanoparticles," and U.S.
Publication No. 2006/0245971 of Burns et al. entitled
"Photoluminescent Silica-Based Sensors and Methods of Use," which
are hereby incorporated by reference in their entireties. A person
skilled in the art will also appreciate that fluorescent
semiconductor nanocrystals, also referred to as quantum dots, can
also be used with the various methods and devices disclosed
herein.
[0030] As indicated above, the present invention provides various
compositions, methods, and devices that use fluorescent
nanoparticles. In one embodiment, fluorescent nanoparticles can be
used to locate, mark, or illuminate tissue. For example, one or
more nanoparticles can be delivered into or onto tissue, including
various body cavities. The nanoparticle(s) can illuminate an area
surrounding the tissue when energy is delivered thereto, or they
can enable the tissue containing the particles to be located. The
nanoparticles can also be used to mark the tissue, thus enabling
future identification and location of the tissue. A person skilled
in the art will appreciate that the particular tissue or body lumen
to be located, marked, or illuminated, as well as the technique for
delivering the nanoparticles to the tissue, can vary and the
following techniques are merely exemplary.
[0031] In one embodiment the nanoparticles can be used to locate a
structure that traverses through other tissue or is otherwise
visually inaccessible. Many tubular structures, such as the ureter,
are not completely visually accessible, but rather traverse through
other tissue and thus are difficult to locate and/or view. Various
regions of the colon can also be difficult at times to access
visually. A solution containing one or more fluorescent
nanoparticles can thus be delivered to the structure of interest to
enable a surgeon to locate the structure. The method of delivery
can vary. For example, the fluorescent nanoparticles can be
disposed in a liquid, foam, or gel solution, such as a saline
solution, and they can be delivered, for example, using an
intravenous (IV) drip or by direct injection into the tissue. Where
the solution has a low viscosity, the structure can be isolated,
e.g., clamped off or otherwise closed, to contain a finite volume
of particles therein, or an open line, such as a saline drip, can
be continuously fed to the structure. Alternatively, the solution
can be modified to have a high viscosity and/or to contain
adhesives. Exemplary solutions will be discussed in more detail
below. Once the solutions is delivered to the structure, energy can
be applied to the area to excite the nanoparticle(s), thereby
enabling the precise location of the particle(s), and thus the
structure containing the particle(s), to be determined.
[0032] In yet another embodiment, the nanoparticles can have a
property that enables them to be filtered into a desired structure,
such as the ureter or colon. In particular, delivery to the kidney
will enable filtration into the ureter, and delivery to the liver
will enable filtration into the colon. For delivery to the ureter
via the kidney, the particles typically have a size in the range of
about 4 nm to 11 nm, whereas the particles typically have a size
that is greater than about 12 nm for delivery to the colon via the
liver. Various delivery techniques can be used, including those
previously discussed, such as IV delivery into the patient's
circulatory system. Once delivered into the body and filtered into
the structure to be located, e.g., the ureter or colon, energy can
be delivered to the vicinity to excite the particle(s), thereby
enabling the precise location of the particle(s), and thus the
structure containing the particle(s), to be determined.
[0033] In yet another embodiment, the nanoparticles can be used to
identify the spread of cancerous cells. With certain types of
cancer, such as breast cancer, the nanoparticles can be injected
into the tumor. The nanoparticles will be carried into other parts
of the body by way of the blood or lymphatic vessels or membranous
surfaces. Energy can thus be delivered to the body to locate the
nanoparticles and thereby identify whether the tumor has spread.
This is particularly useful in determining whether cancerous cells
have reached the sentinel lymph node. The use of nanoparticles
formed from a fluorophore center core and a biocompatible shell is
also advantageous as it provides a non-toxic method for locating
cancerous cells, unlike prior art methods which utilize
radio-isotopes and semi-conductive nanoparticles which contain
toxic metals.
[0034] A person skilled in the art will appreciate that the
aforementioned techniques can be used to locate any structure. By
way of non-limiting example, other exemplary structures include the
structures in the biliary system, the lymphatic system, and the
circulatory system.
[0035] The present invention also provides methods for marking
tissue. In one embodiment, the nanoparticles, or a solution
containing one or more nanoparticles, can be applied or "painted"
onto a tissue surface, or injected into tissue. The applied
nanoparticles can function as a marking used to allow for
subsequent identification of the tissue. For example, during a
colonoscopy the nanoparticles can be applied to or near a polyp
that cannot be removed during the procedure. During a subsequent
procedure, the nanoparticles can be excited with energy and used to
locate and identify the polyp, for example from the abdominal
perspective. The markings can also be used to indicate orientation.
For example, directional markings, such as arrows or other lines,
can be made with the nanoparticles. Various applicators, such as a
paint brush or similar applicator, can be used, and an exemplary
applicator will be discussed in more detail below. In another
embodiment, the markings can be used to detect leaks, for example
in a closed system fluid based implant, such as with gastric bands.
One failure mode experienced with gastric band is that the system
can leak due to punctures of the catheter with a needle during an
adjustment, undetected puncturing of the balloon with a suture
needle during surgery, and partially or completely disconnected
catheter-to-port connections. The fluorescent nanoparticles can be
delivered to the band, e.g., in a solution, and their disappearance
from the band system or their location outside of the band system
in the body can be used to indicate the presence of a leak.
[0036] In another embodiment, fluorescent nanoparticles can be used
to illuminate tissue. For example, the nanoparticles can be applied
to a tissue surface in a body cavity to illuminate the body cavity,
such as the stomach, uterus, abdominal cavity, thoracic cavity,
vaginal canal, nasal passages, and ear canal. By way of
non-limiting example, the nanoparticles can be disposed within a
gel, such as KY.RTM. Jelly, carboxy methyl cellulose, collagen, or
hydrogel, and delivered to the uterus by brushing or otherwise
applying the particles to an inner surface of the uterus. Upon
energy delivery, the nanoparticles are effective to illuminate the
uterus, thereby facilitating viewing during a hysterectomy or other
procedures. Similarly, the nanoparticles can be applied to an area
of tissue within the stomach to thereby illuminate the stomach
during various procedures. A person skilled in the art will
appreciate that the nanoparticles can be used to illuminate
virtually any body cavity.
[0037] As indicated above, various devices can be used to apply the
particles to a tissue surface, including rigid and flexible
devices, such as elongate shafts, syringes, or hand held pens with
marking tips configured to coat, inject, or otherwise deliver the
nanoparticles to tissue. The markings can also be applied manually
using ones finger tips. FIG. 2 illustrates one exemplary embodiment
of a marking device 20. As shown, the marking device 20 has an
elongate shaft 22 with a distal tip 24. The elongate shaft 22 can
have a variety of configurations, and the particular configuration
can vary depending on the mode of insertion. In the illustrated
embodiment, the elongate shaft 22 is disposed through a cannula
having a working channel that extends into a body cavity. The
elongate shaft 22 can also include one or more lumens formed
therein and extending between proximal and distal ends thereof. The
lumens can be used to deliver a nanoparticle solution to the distal
tip 24. The distal tip 24 can also have a variety of
configurations. In the illustrated embodiment, the distal tip 24
has a nozzle formed thereon for spraying the nanoparticles onto a
tissue surface. In other embodiments, the tip 24 can include a
brush for brushing the particles onto a tissue surface. Again, the
particular configuration can vary depending on the intended
use.
[0038] In use, as indicated above, the marking device 20 can be
inserted through the trocar 26 that extends through a tissue
surface and into the abdominal cavity. Endoscopes or other access
devices can also optionally be used, and/or the device can be
introduced through a natural orifice or through a man-made orifice.
Once positioned adjacent to a target tissue, the marking device 20
can be manipulated using, for example, controls to articulate the
distal end of the device and controls to actuate the nozzle, to
apply the nanoparticles to the tissue surface. A person skilled in
the art will appreciate that a variety of marking devices known in
the art can be used. By way of non-limiting example, U.S. patent
application Ser. No. 11/533,506 of Gill et al., filed on Sept. 20,
2006 and entitled "Dispensing Fingertip Surgical Instrument," which
is incorporated herein by reference in its entirety, discloses one
exemplary embodiment of a marking device that can be used to apply
nanoparticles to a tissue surface.
[0039] In each of the various embodiments disclosed herein the
nanoparticles can optionally be delivered in a carrier. The
particular composition of the carrier can vary, and suitable
carriers include any biocompatible liquid, foam, gel, or solid. The
carrier and/or the nanoparticles can also include other substances,
such as pharmaceutical and/or therapeutic substances. In one
exemplary embodiment a more viscous liquid, foam, or gel is used to
prevent or delay the particles from being flushed from the tissue
site. Exemplary high viscosity liquids include, by way of
non-limiting example, KY.RTM. Jelly, carboxy methyl cellulose,
collagen, and hydrogel. The solution can also optionally have
adhesive properties to help retain the nanoparticles in a desired
location. Exemplary adhesives are disclosed, by way of non-limiting
example, in U.S. Publication No. 2004/0190975 of Goodman entitled
"Applicators, Dispensers and Methods for Dispensing and Applying
Adhesive Material," which is hereby incorporated by reference in
its entirety. This reference also discloses various exemplary
applicator devices that can be used to deliver nanoparticles to
tissue. The nanoparticles can also be combined with existing
marking fluids, such as biocompatible dyes, stains, or colored
adhesives. A person skilled in the art will appreciate that any
carrier can be used.
[0040] The composition of the fluorescent nanoparticles can also
vary to provide different functions. In one embodiment, a
combination of visible and non-visible dyes can be used to form
fluorescent nanoparticles for use in marking tissue. Such dual- or
multi-wavelength nanoparticles can be delivered to tissue and, once
delivered, the visible dyes can be used to quickly locate a tissue
containing the particles and the non-visible dyes can provide more
precise viewing. By way of non-limiting example, nanoparticles
containing visible and non-visible dyes can be delivered to the
ureter. Visible dyes located near the surface can be viewed with
visible light to help locate the ureter. Once located, an infrared
light can be used to see the non-visible dye locating the ureter
path located deeper within tissue. Exemplary viewing methods will
be discussed in more detail below. While visible fluorescent dyes
are preferred, other types of visible dyes may be used in
combination with non-visible fluorescent nanoparticles.
[0041] In other embodiments, the composition can be adapted to
provide a therapeutic effect. For example, a magnetic material can
be used with the fluorescent nanoparticles to enable therapeutic
energy to be delivered to tissue. Various techniques can be used to
associate a magnetic material with the nanoparticles. For example,
the particles can be manufactured with a magnetic or
magnetic-containing core. Alternatively, the particles can be
coated with a magnetic material, or they can be disposed within a
magnetic solution. Exemplary magnetic materials include, by way of
non-limiting example, iron compounds such as Fe(OH).sub.2 or
compounds containing Fe.sup.+2 or Fe.sup.+3 ions. In use, the
magnetic nanoparticles can be applied to tissue to be treated using
various methods, including those previously discussed. The location
of the particles can be identified using light, and once identified
an alternating current can be delivered to the particles to induce
inductive heating. As a result, the magnetic nanoparticles will
generate heat, thereby cauterizing or otherwise treating the
tissue. The use of magnetic particles in combination with
fluorescent nanoparticles is particularly advantageous as the
fluorescent nanoparticles enable precise identification of the
tissue being treated, thereby limiting or avoiding damage to
healthy tissue.
[0042] In another embodiment, a sensor can be provided for sensing
the tissue temperature to enable a desired temperature range to be
maintained during energy delivery. The sensor can be disposed on a
distal end of a device, such as an endoscope, catheter, or other
delivery device, and it can be coupled to an external apparatus
that displays the measured temperature. In certain exemplary
embodiments, the temperature of the tissue being treated is brought
to a temperature above about 150.degree. F. The magnetic particle
property may also be used to steer the particle to a preferred
location or to cause the particles to accumulate at a preferred
location. For example, a magnet can be positioned in the vicinity
of the particles, for example, adjacent to an external tissue
surface, and the magnet can be manipulated to cause the particles
to move in a desired direction.
[0043] In another embodiment, fluorescent nanoparticles can be used
on medical devices to indicate the location and/or orientation of
the device once introduced into a patient's body, or to illuminate
a body cavity within which the device is disposed. For example,
fluorescent nanoparticles can be coated onto, embedded within, or
disposed within an implant to enable future location and
identification of the implant. The particles, or a liquid or solid
containing the particles, can also be disposed within a capsule or
other structure, and that structure can in turn be disposed within
an implant. By way of non-limiting example, the nanoparticles can
be placed around a port, such as a bolus port in a drug pump or a
fluid-refill port in a gastric band. FIG. 3A illustrates a drug
delivery pump 30 having a bolus port 31 with nanoparticles 32
disposed therearound. The nanoparticles can be used to locate the
port and allow easy access for introducing and removing fluids to
and from the port. For example, FIG. 3B illustrates the
nanoparticles radiating through the tissue to enable location of
the port, thereby allowing a syringe, as shown, to be inserted into
the port. A reading unit with a fluorescence meter can be used to
identify and locate the particles and thus the port. The
nanoparticles can also be used to indicate size and/or directional
orientation. For example, the nanoparticles can be located around a
gastric band, either by coating the particles onto the band,
embedding the particles in the band during manufacturing, or
filling the band with a nanoparticle-containing solution. FIG. 4
illustrates a gastric band 40 having a balloon disposed along the
length thereof and containing nanoparticles or a nanoparticle
solution 42. In use, the gastric band 40 is positioned around the
stomach to decrease the size of the stomach. The nanoparticles in
the band 40 can be viewed to determine the size or diameter of the
gastric band 40, thereby enabling a surgeon to easily determine
whether any adjustments are necessary. If the band 40 is too small
or too large, fluid can be added to or removed from the band
40.
[0044] In yet another embodiment, a catheter, endoscope, or other
devices that are introduced into body can have nanoparticles
positioned to allow the location of a distal end of the device to
be identified during use, to indicate a directional orientation of
the device, and/or to illuminate an area surrounding a portion of
the device. By way of non-limiting example, FIG. 5A illustrates an
elongate shaft 50, such as a catheter or endoscope, having
nanoparticles 52 disposed around a distal end thereof to illuminate
tissue surrounding the distal end of the device 50. The use of
nanoparticles for illumination is particularly advantageous as it
eliminates the need for a separate light source on the device. The
particles could also be positioned to form indicia that indicate a
directional orientation or physical end of the device. For example,
FIG. 5B illustrates an elongate shaft 54, such as a catheter or
endoscope, having particles disposed on the device so as to form a
series of parallel lines 56 along a length of the distal end of a
device 54. The lines 56 can thus be used to indicate the insertion
depth of the distal end of the device 54 into a body lumen or to
provide a reference for use with anatomical features. The lines
could also be in the form of a bar code containing data, such as
the manufacturer, lot code, or date of manufacture, that can be
obtained from the device without having to remove the device from
the body. The nanoparticles could also be disposed to form one or
more directional indicators, such as an arrow 58 as shown in FIG.
5C, that enables a surgeon to determine the particular directional
orientation of the device within a body lumen or cavity. In yet
another embodiment, the nanoparticles can be located or, disposed
within, or embedded in an absorbable material, such as a suture or
fastener, that would leave the nanoparticles in the tissue after
the absorbable material is absorbed. A person skilled in the art
will appreciate that various techniques can be used to position one
or more nanoparticles on or in a device or implant.
[0045] Various exemplary methods and devices are also provided to
excite the fluorescent nanoparticles to enable viewing. In an
exemplary embodiment, electromagnetic energy can be delivered to
fluorescent nanoparticles disposed within a patient's body using a
delivery apparatus, such as an endoscope or laparoscope. The
delivery apparatus can be located externally, e.g., above the
tissue surface, or internally. The excitation source can include
any device that can produce electromagnetic energy at wavelengths
that correspond to the absorption cross-section of the
nanoparticles, including but not limited to, incandescent sources,
light emitting diodes, lasers, arc lamps, plasma sources, etc.
Various imaging technologies can also be used for detecting,
recording, measuring or imaging fluorescent nanoparticles. In an
exemplary embodiment, the imaging technology is adapted to reject
excitation light, detect fluorescent light, form an image of the
location of the nanoparticles, and transmit that image to either a
storage or display medium. Exemplary devices include, for example,
a flow cytometer, a laser scanning cytometer, a fluorescence
micro-plate reader, a fluorescence microscope, a confocal
microscope, a bright-field microscope, a high content scanning
system, fiber optic cameras, digital cameras, scanned beam imagers,
analog cameras, telescopes, microscopes and like devices.
[0046] In an exemplary embodiment, the energy source is light,
i.e., electromagnetic radiation, and the reading apparatus has an
elongate shaft that is adapted to be inserted into a body lumen and
that includes a light emitting mechanism and an image receiving
apparatus. Since fluorescent nanoparticles formed from a
fluorophore core and a silica shell can absorb and emit energy in
the visible, infrared, and near infrared frequencies, and they are
illuminated at one wavelength and observed at a different shifted
wavelength, it is desirable to provide an imaging apparatus that
can enable visualization of such nanoparticles. FIG. 6 illustrates
one exemplary embodiment of a laparoscope 60 that has two
illumination or light emitting sources, generically illustrated as
elements 61A, 61B. As shown, the laparoscope 60 utilizes an optical
switch 62 to select the illumination source(s). One illumination
source may be a standard white light source, such as a Xenon arc
lamp used in standard endoscopic systems for illuminating and
viewing in the visible spectrum. The second light source may be a
narrow-band source associated with the absorbance cross-section of
the nanoparticles, such as a laser, LED, mercury source, or
filtered broadband source. One exemplary narrow-band source is a
780 nm pigtailed laser diode. The optical switch 62 can connect the
selected source 61A, 61B to an optical fiber bundle (not shown)
that extends through the laparoscope 60 for transmitting the light
through an eyepiece at the distal end of the laparoscope 60. When
the light is transmitted, e.g., by depressing a switch, button, or
foot pedal, generically illustrated as element 64, the fluorescent
nanoparticles N on the tissue will excite and fluoresce. The
laparoscope 60 can also include an image receiving apparatus or
camera 66 for collecting the reflected light from the fluorescent
nanoparticles, and a filter switch 68 to place the appropriate
optical filter between the eyepiece and the camera 66. The filter
that is used for visualization of the nanoparticles N, for example,
must be highly efficient at rejecting the excitation wavelength in
order to avoid saturation of the camera 66, while still being
highly transparent at the wavelength of the emission of the
nanoparticles N. One exemplary filter is an interferometric
long-pass filter with four orders of magnitude of rejection at the
excitation wavelength and over 80% transmission at the peak of the
fluorescent band. As further shown in FIG. 6, the captured image
can be transmitted to a monitor 69 that is coupled to the camera 66
by a camera control box 67. The monitor 69 can be an on-board
monitor or an external monitor, as shown, or other reading devices
can be used such as a readout display, an audible device, a
spectrometer, etc. A person skilled in the art will appreciate
that, while a laparoscope 60 is shown, various other elongate
shafts, such as catheters and endoscopes, can be used to transmit
and receive light for viewing fluorescent nanoparticles. The
embodiment described illustrates real time viewing. A person
skilled in the art will also appreciate that image(s) can be
captured and stored for overlay transmission, such as showing a
peristaltic pulse as a continuous path.
[0047] Additional utilization can also be achieved in the
non-visible ranges, as previously indicated, by combining a visible
light source with a non-visible light source enabling the ability
to turn the non-visible image on or off. The images may be viewed
either side by side or simultaneously by overlapping the images.
The visible light source can vary and can be an ambient room
source, an LED, a laser, a thermal source, an arc source, a
fluorescent source, a gas discharge, etc., or various combinations
thereof. The light source can also be integrated into the
instrument or it may be an independent source that couples to the
instrument.
[0048] FIG. 7A illustrates one embodiment of a laparoscope 70 that
has the ability to overlay a fluorescent image onto a visible image
to enable simultaneous viewing of both images. In this embodiment,
both light sources, generically illustrated as 71a and 71b, can be
combined into an illumination port of the laparoscope 70 using, for
example, a bifurcated fiber (not shown). At the eyepiece of the
scope 70 (located at the proximal end), a specialized optical fiber
can be used to split the light to two separate cameras, generically
illustrates as 76a and 76b. For example, a filter can reflect all
visible light to a visible image camera 76a and can transmit all
other light for receipt by the fluorescent camera 76b. A second
interference filter can be placed in the transmitted path to direct
only fluorescent waveband to the fluorescent camera 76b. Both
camera outputs can be combined using an image combiner, generically
illustrated as 78, and the images can be overlaid using techniques
well known in the art to display, e.g., on a monitor 79, a
simultaneous image. In an exemplary embodiment, the fluorescent
image can be color-shifted to stand out relative to the visible
display.
[0049] FIG. 7B shows yet another embodiment where the
above-described capability can be incorporated into a hand held
instrument with a self-contained monitor or display output that can
feed to other displays, such as those noted above. In particular,
FIG. 7B illustrates a device 70' having two illumination or light
emitting sources, generically illustrated as elements 71a', 71b',
that are located within a housing having a monitor or display 79'
located on the proximal-most end thereof The light sources 71a',
71b' can be similar to those previously described above with
respect to FIG. 6, and the housing can also include other features,
such as a filter switch, an optical switch, etc., as previously
described above. In use, light can be delivered to tissue to cause
the nanoparticles to fluoresce. As shown in FIG. 7B, an infrared
excitation beam is delivered to a ureter U having several
nanoparticles therein, and the image is viewed on the on-board
display 79'.
[0050] FIG. 8A illustrates one exemplary embodiment of an adaptor
80 for enabling a conventional laparoscope or endoscope to view
fluorescent nanoparticles. A person skilled in the art will
appreciate that while an endoscope is shown, the adaptor can be
used on any type of scope, including scopes used during open,
endoscopic, and laparoscopic procedures. As shown, the adaptor 80
generally includes first and second members, e.g., an extension
eyepiece 82 and a mating element 86, that are adapted to capture an
endoscope eyepiece 100 therebetween. The adaptor 80 can also be
configured to seat a filter 84 therein between the endoscope
eyepiece 100 and the extension eyepiece 82. The extension eyepiece
82 can have a variety of configurations, but in an exemplary
embodiment the extension eyepiece 82 is adapted to extend the
eyepiece on the proximal end of a standard scope. As shown in FIG.
8A, the extension eyepiece 82 has a generally cylindrical shape
with a viewing window or lumen 83 formed therethrough and adapted
to be aligned with the viewing window or lumen 103 formed in the
eyepiece 100 of a scope. The extension eyepiece 82 can also include
an enlarged region 82a having a diameter d.sub.1 greater than a
diameter d.sub.1 of the endoscope eyepiece 100 to allow the
enlarged region 82a to be disposed around at least a portion of the
endoscope eyepiece 100. As further shown, the extension eyepiece 82
can include a cavity formed therein for seating the filter 84, as
shown. The illustrated cavity is formed in the enlarged diameter
region, and it extends across the path of the lumen 83 such that
the filter 84 will extend across and between the viewing path of
the eyepieces 82, 100 to thereby filter light viewed through the
eyepieces 82, 100. The filter 84 can be used to block out visible
light, thereby enabling clear viewing of the non-visible
wavelengths. As further shown, the adaptor 80 can also include a
mating element 86 for mating the extension eyepiece 82 to the
endoscope eyepiece 100. While various mating elements can be used,
in the illustrated embodiment the mating element 86 is in the form
of a ring having a lumen extending therethrough with an enlarged
cavity 86c formed in a proximal end 86p thereof for receiving an
enlarged diameter portion 100a formed on the proximal end of the
eyepiece 100. The mating element 86 can be loaded onto the eyepiece
100 by removing the eyepiece 100 and sliding the mating element 86
over the distal end 100d of the eyepiece 100. As a result, the
eyepiece 100 will be positioned between the mating element 86 and
the extension eyepiece 82. The mating element 86 can also include
threads 82t formed on an outer surface thereof for mating with
threads 86t formed within a cavity in a distal end of the extension
eyepiece 82. Thus, the mating element 86 can be disposed around the
eyepiece 100 and threaded into the extension eyepiece 82 to engage
the enlarged diameter portion of the endoscope eyepiece 100, as
well as the filter 84, therebetween. The extension eyepiece 82 can
also include one or more seals disposed therein to cushion the
filter when the mating element 86 is threaded onto the extension
eyepiece 82. FIG. 8A illustrates first and second seals 85a, 85b,
such as o-rings, disposed within grooves formed in the extension
eyepiece adjacent to superior and inferior surfaces of the filter
84. The seals 85a, 85b are positioned radially around the superior
and inferior surfaces of the filter 84, and in use when the mating
element 86 is threaded onto the extension eyepiece 82, the seals
85a, 85b will cushion the filter 84 as the scope eyepiece 100 abuts
against the bottom seal 85b.
[0051] In other embodiments, where the eyepiece on the endoscope is
not removable, the mating element can be formed from two halves
that mate together to allow the mating element to be positioned
around the eyepiece. FIG. 8B illustrates one embodiment of a mating
element 86' having two halves 86a', 86b' that mate together. In the
illustrated embodiment, the two halves 86a', 86b' are hingedly
connected, however they can optionally be totally separable from
one another. The mating element halves 86a', 86b' can also include
other features to facilitate alignment of the halves with one
another. For example, the two halves can include a pin and bore
connection, as shown, for aligning the two halves. An alignment
mechanism is preferred in order to align the threads on the two
halves to enable threading of the mating element into the extension
eyepiece. A person skilled in the art will appreciate that the
mating element and the extension eyepiece can be mated using a
variety of other mating techniques, such as a snap-fit connection,
a luer lock, an interference fit, etc.
[0052] In another embodiment, the filter can be removable. FIG. 9
illustrates one such embodiment of an extension eyepiece 82' having
a removable filter cartridge 87'. As shown, the extension eyepiece
82' includes a cut-out or slot 88' extending therethrough and
across the viewing lumen 83'. The slot 88' is configured to
slidably and removably receive a filter cartridge 87' such that a
filter 89' held within the filter cartridge 87' is aligned with the
viewing lumen 83' in the extension eyepiece 82' to thereby filter
light passing therethrough. The filter cartridge 87' can thus be
removed and replaced with another filter cartridge 87', or
alternatively the filter 89' in the filter cartridge 87' can be
replaced to enable different types of filters to be disposed within
the extension eyepiece 82'. In an exemplary embodiment, as shown,
the filter cartridge 87' includes two side-by-side slots for
seating two filters (only one filter 89' is shown, the other filter
is disposed within the eyepiece 82'). The filter cartridge 87' can
also include a hole 81' formed in each end thereof for receiving a
pin (not shown) that is configured to function as a stop to
selectively align each filter with the viewing lumen as the filter
cartridge 87' is slid back and forth.
[0053] As previously discussed with respect to FIG. 8A, the
cartridge 87' can also include one or more seals disposed therein.
In this embodiment, the seals are particularly effective for
preventing incident light from entering into the viewing lumen
through the slot 88'. The seals can also assist in aligning the
filters with the eyepiece 82'. For example, as shown in FIG. 8B,
the cartridge 87' can include a groove 85' formed therein around
the filter 89'. While not shown, grooves can be formed on both the
top and bottom surfaces of the cartridge 87', and around both
filters such that the cartridge includes a total of four grooves.
The cartridge 87' can also include one or more seals (not shown),
such as o-rings, disposed therein. When the cartridge 87' is slid
into the slot 88' in the eyepiece 82', the seals will extend into
and engage the grooves extending around the filter, thereby
aligning the filter with the viewing lumen in the extension
eyepiece and also preventing incident light from entering the
viewing lumen. A person skilled in the art will appreciate that a
variety of other techniques can be used to provide an
interchangeable filter. For example, a kit containing multiple
adaptors, or multiple extension eyepieces, having different filters
can be provided.
[0054] One skilled in the art will appreciate further features and
advantages of the invention based on the above-described
embodiments. Accordingly, the invention is not to be limited by
what has been particularly shown and described, except as indicated
by the appended claims. All publications and references cited
herein are expressly incorporated herein by reference in their
entirety.
* * * * *