Patent Publication Number: US-2009217932-A1

Title: Intraluminal tissue markers

Description:
FIELD OF THE INVENTION 
     The present invention relates to intraluminal tissue markers and methods for marking tissue intraluminally. 
     BACKGROUND OF THE INVENTION 
     Colonoscopy is an outpatient procedure in which the rectum and the inside of the lower large intestine (colon) are examined. Colonoscopies are commonly used to evaluate bowel disorders, rectal bleeding or polyps (usually benign growths) found on contrast x-rays. Colonoscopies are also performed to screen people over age 50 for colon and rectal cancer. During a colonoscopy, a physician uses a colonoscope (a long, flexible instrument about ½ inch in diameter) to view the lining of the colon. The colonoscope is inserted through the rectum and advanced to the large intestine. 
     If necessary during a colonoscopy, small amounts of tissue can be removed for analysis (called a biopsy) and polyps can be identified and removed. In many cases, colonoscopy allows accurate diagnosis and treatment without the need for a major operation. However, in some cases the tissue cannot be removed during the colonoscopy, and thus must be removed in a subsequent surgical procedure. In these situations, india ink or blue dye is topically injected during the preoperative colonoscopy to mark the tumor site. However, such a procedure includes the intrinsic danger of possibly injecting dye into the peritoneal cavity. In addition, the injected marker may also spread so widely that the intended site may become obscured. 
     Accordingly, there remains a need for improved methods and devices for marking tissue, such as the bowel wall. 
     SUMMARY OF THE INVENTION 
     The present invention generally provides methods and devices for marking tissue to be subsequently located for removal from a body or for other examination. In one aspect, a method for marking tissue is provided that includes delivering a marking solution to tissue. The marking solution can have a first component that forms a visible marking on a surface of the tissue and a second component that forms a palpably identifiable tactile marking on the tissue. The marking solution can have a variety of compositions. In some embodiments, at least one of the first and second components can include two chemicals that react to form a marking when the marking solution is delivered to the tissue. The marking solution can be delivered to tissue using a variety of devices, alone or in combination. The visible marking can be identified in a variety of ways, such as by being visible to the naked eye, with or without exposure to an excitation source. In some embodiments, the visible marking can have a wavelength in a non-visible range. 
     In another aspect, a method for marking tissue includes positioning a device containing a marking solution proximate to a target tissue in a patient&#39;s body and delivering the marking solution from the device to the target tissue to form a visual mark on the tissue with a first component of the marking solution and to form a palpably identifiable tactile marking on the target tissue with a second component of the marking solution. The marking solution can be delivered to the tissue in a variety of ways. For example, at least a portion of the marking solution can be delivered into a subdermal layer of tissue proximate to the target tissue. In some embodiments, delivering the marking solution from the device can cause the first and second components to mix together. 
     The method can also include removing the device from the patient&#39;s body and locating the target tissue by palpably identifying the tactile marking and/or by visually identifying the visual mark on the target tissue. Locating the target tissue can optionally include delivering energy to the target tissue to visually identify the marked tissue. In some embodiments, delivering energy to the target tissue can cause the visual mark to fluoresce. 
     In another aspect, a tissue marking system is provided. The system includes a marking solution containing a first component that can form a visible marking on a surface of tissue and a second component that can form a palpably identifiable tactile marking under the surface of the tissue. In some embodiments, the visible marking can have a wavelength in a non-visible range. The marking solution can have a variety of compositions. In one embodiment, at least one of the first and second components can include two chemical components that are mixed together to form a marking when the marking solution is injected into tissue. In an exemplary embodiment, the marking solution can include an active ester in N-methylpyrrolidone. In another embodiment, the first component can include an electrophile monomer in N-methylpyrrolidone and a dye, and the second component can include a nucleotide polymer in water. 
     In other aspects, the marking solution can be contained within a delivery device that can inject the marking solution into tissue. The delivery device can have a variety of configurations. For example, the delivery device can have a needle disposed at its distal end for injecting the marking solution into tissue. The delivery device can also have a first chamber containing the first component and a second chamber containing the second component. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The invention will be more fully understood from the following detailed description taken in conjunction with the accompanying drawings, in which: 
         FIG. 1  is a perspective view of one embodiment of an introducer device having a delivery device disposed therein that can deliver a marking solution to a tissue; 
         FIG. 2  is a perspective view of the delivery device of  FIG. 1  delivering a marking solution to a tissue; 
         FIG. 3  is a perspective, partially cross-sectional view of one embodiment of a single-chamber syringe; 
         FIG. 4  is a perspective, partially cross-sectional view of one embodiment of a double-chamber syringe; 
         FIG. 5  is a perspective, partially cross-sectional view of one embodiment of a double-barrel syringe; 
         FIG. 6  is a perspective, partially cross-sectional view of one embodiment of a double-barrel syringe having a mixing chamber; 
         FIG. 7  is a cross-sectional schematic view of one embodiment of a needle disposed in a housing; 
         FIG. 8  is a cross-sectional schematic view of the needle of  FIG. 7  extending beyond a distal end of the housing; 
         FIG. 9  is a schematic view of one embodiment of a needle tip; 
         FIG. 10  is a schematic view of another embodiment of a needle tip; 
         FIG. 11  is a perspective view of one embodiment of an introducer device having a delivery device disposed therein and delivering a marking solution to tissue; 
         FIG. 12  is a perspective view of the tissue of  FIG. 2  with the marking solution delivered thereto; 
         FIG. 13  is a cross-sectional view of one embodiment of an introducer device disposed within a body lumen and a marker marking a tissue in the body lumen; 
         FIG. 14  is a cross-sectional view of the marker of  FIG. 13  being palpably located in the body lumen; and 
         FIG. 15  is a diagram illustrating one embodiment of a laparoscopic system for viewing a fluorescent marker. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     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. 
     The present invention generally provides methods and devices for marking a target tissue to be subsequently located for removal from a body, for diagnosis, for treatment, or for other purposes. While the methods and devices disclosed herein can be used in conventional, open surgical procedures and hand assisted laparoscopic surgery (HALS), they are particularly useful in minimally invasive surgical procedures, such as endoscopic and other laparoscopic procedures. The principles described herein can be applicable to the particular types of tools described herein and to a variety of other surgical tools having similar functions. In addition, the tools can be used alone in a surgical procedure, or they can be used in conjunction with other devices that facilitate the surgical procedure. A person skilled in the art will appreciate that the present invention has application in conventional open surgical instrumentation as well as application in robotic-assisted surgery. 
     In general, a marker is provided that can be delivered to a target tissue desirable for marking, e.g., for removal from a body or for other examination. The target tissue can include tissue to be treated, diagnosed, removed, geographically marked, or otherwise examined, as well as tissue proximate to tissue to be treated, diagnosed, removed, geographically marked, or otherwise examined. In an exemplary embodiment, the marker can include a solution that can form a visual marking and a palpably identifiable tactile marking on the target tissue. The marker can remain in the body and be subsequently visually and/or palpably identified to locate the target tissue. In this way, the marker can provide flexibility and ease in locating the target tissue because the marker can be identified using various techniques. Being able to identify the marker in more than one way can also provide identification confirmation and improve certainty in determining a marker&#39;s location. The visual and tactile markings can help improve chances of locating the target tissue because if one of the visual and tactile markings fades, reduces in area or volume, becomes bioabsorbed, becomes obscured or damaged by tissue or fluid in the body, “bleeds” into surrounding tissue, or changes in any other way to affect its ability to be located, then the other one of the markings can still be used to locate the target tissue. Furthermore, the marker can provide markings on both a surface of the target tissue and within tissue, e.g., in a subdermal layer, thereby improving the marker&#39;s chances of identification over time because the marker can be less likely to become obscured or damaged both on the tissue&#39;s surface and within the tissue. While the marker can be used to mark any tissue for any purpose, in an exemplary embodiment the marker is configured for delivery through the working channel of a delivery device and for use in marking tissue for removal from the body, e.g., a lesion, a polyp, or other tissue growth or unhealthy tissue identified during a colonoscopy and intended to be removed from the bowel wall during a subsequent surgical procedure. In another exemplary embodiment, the marker can be used to geographically mark tissue to indicate a surgical procedure site, e.g., a location of biopsied tissue. In yet another exemplary embodiment, two or more markers can be delivered to define a line or an area indicating the target tissue. 
     The marking solution can have a variety of compositions. In an exemplary embodiment the marking solution can include two components, one component to visually mark a tissue and another component to tactilely mark the tissue. The visually-marking and tactilely-marking components can each be formed from a variety of materials, preferably biocompatible materials safe for use in the body. The marking solution and its components are preferably fluids, although one or more of the marking solution and its components can include any combination of solids or partial solids (e.g., a gel), either before or after delivery to a target tissue. 
     The visually-marking component of the marking solution can include one or more materials configured to be applied to a tissue and be visually identifiable on, including through, the tissue&#39;s surface. The material used for the visually-marking component can be a one-part solution configured to provide a visual marking, or it can be a multiple-part solution including a dye added to another chemical. The dye can include any material configured to be visually identifiable on and/or through a tissue surface with or without application of energy, as discussed further below. Non-limiting examples of dye include D&amp;C Violet No. 2, ink, or other visible color dye (e.g., a dye having a wavelength within the visible range, i.e., from about 400 mm to 700 nm), an infrared dye (e.g., a dye having a wavelength near or within the infrared range, i.e., from about 600 nm to 1350 nm), a fluorescent nanoparticle, and any other dye known in the art. Using a dye having a wavelength outside the visible range can help reduce chances of the dye obscuring the color or stasis of the target tissue. In an exemplary embodiment, the visually-marking component can include an electrophile monomer at 10% solids in N-methylpyrrolidone (NMP) and D&amp;C Violet No. 2 incorporated into the electrophile monomer in NMP. Other non-limiting examples of the visually-marking component include D&amp;C Violet No. 2 and a 10%, a 38%, or a 60% solution of an active ester compound in NMP, Cy 5.5 (fluorescing dye) manufactured by GE Healthcare, Chalfont St. Giles, United Kingdom, and Indocyanine Green (fluorescing dye) manufactured by Acros Organics N.V., Geel, Belgium. 
     In one exemplary embodiment, the visually-marking component can include a fluorescent nanoparticle, which may require light for visibility. 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. application Ser. No. 11/771,490 of Voegele et al. filed Jun. 28, 2007 and entitled “Nanoparticle Tissue Based Identification and Illumination,” 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. 
     The tactilely-marking component of the marking solution can also include one or more materials configured to be delivered to a tissue and be tactilely identifiable on the tissue&#39;s surface or through the tissue&#39;s surface. In an exemplary embodiment, the tactilely-marking component can include a nucleotide polymer in water, e.g., a nucleotide polymer at 10% solids in water. Other non-limiting examples of the tactilely-marking component include a 10% solution of amino dextran in water, a 15% solution of Di-lysine in water and triethylamine, and a 72.4% solution of Hexamethylene diamine in water. 
     By way of non-limiting example only, the marking solution, including both visually-marking and tactilely-marking components can include a first composition of a 10% solution of an active ester compound in NMP and D&amp;C Violet No. 2, and a second composition of a 10% solution of amino dextran in water, with the first and second compositions mixed in a 1:1 volume or weight ratio. In another non-limiting example, the marking solution can include a first composition of a 38% solution of an active ester compound in NMP and D&amp;C Violet No. 2, and a second composition of a 15% solution of Di-lysine in water and triethylamine. As still another non-limiting example, the marking solution can include a first composition including a 60% solution of an active ester compound in NMP and D&amp;C Violet No. 2, and a second composition of a 72.4% solution of Hexamethylene diamine in water, with the first and second compositions mixed in a 7:2:1 ratio that can form a solid gel immediately upon mixing. 
     The visually-marking component and/or the tactilely-marking component can be adjusted or can include one or more additional components for achieving a desirable level of various properties, such as image enhancement, drug delivery, viscosity, drying time, reflectivity, fluorescence, contrast (transparency), bioabsorption, sterilization response, shelf life, storage conditions, biocompatibility, temperature response, sealant properties, bi-product properties, metering control, surface condition response, and/or adherence to, penetration of, or bonding to tissue. 
     The marker can be delivered to a target tissue in a variety of ways. In an exemplary embodiment shown in  FIG. 1 , a delivery device  10  having a marking solution disposed therein can be advanced through a working channel  12  of an introducer device  14  and positioned proximate to a target tissue. While  FIG. 1  illustrates the marker used to identify a tissue growth  18  on a surface  16  of a tissue  20 , e.g., an organ, the marking solution can be used to mark any tissue anywhere within the body, e.g., within a tubular structure (such as the lower large intestine or any other body lumen), on and/or beneath a surface of an organ, etc. As shown in  FIG. 2 , a marking solution  22  can be delivered to the tissue  20  from a distal end  24  of the delivery device  10 . The marking solution  22  can visually and tactilely mark the tissue  20  such that the marker can be identified in a plurality of ways. The marking solution  22  can be delivered to the tissue  20  in a variety of ways, such as by injection, application to a surface, and/or delivery in any other way appreciated by a person skilled in the art. The marking solution  22  can, but need not, penetrate the tissue&#39;s surface  16 , e.g., into the tissue&#39;s subdermal layer  26 . Furthermore, the marking solution  22  can be delivered to the tissue&#39;s surface  16  and at least partially naturally permeate into the tissue  20 , e.g., into the subdermal layer  26  by absorption. In this way, the marking solution  22  can provide a surface marking on the tissue  20  and/or a marking under the surface  16  of the tissue  20 , thereby allowing the tissue growth  18  to be located by one or both of the surface and sub-surface markings. 
     The marking solution  22  is illustrated as being delivered by the delivery device  10  advanced through the introducer device  14  and applied to the tissue&#39;s surface  16 , but a variety of delivery devices and introducer devices can be used to deliver any amount of a marking solution to a tissue. In the event that the marker is application during a colonoscopy, the introducer can be any flexible, elongate colonoscope, endoscope, or other device that is capable of being inserted into the body, such as through a natural orifice, through a puncture hole formed in tissue, and in any other way appreciated by a person skilled in the art. The delivery device  10  can be any device that is effective to contain the marking solution and deliver it to the tissue  20 . The delivery device  10  can also be configured to pass through the working channel  12  of the introducer device  14 . However, in other embodiments, the delivery device  10  and/or introducer device  14  can be used alone to deliver the marking solution. 
       FIGS. 3-6  illustrate various exemplary delivery devices that can inject a marking solution onto or into tissue.  FIG. 3  illustrates one embodiment of a single-chamber syringe  30  for delivering a marking solution  28  onto and/or into a tissue. Visually-marking and tactilely-marking components of the marking solution  28  can be delivered as a pre-mixed solution from the single-chamber syringe  30 . The visually-marking and tactilely-marking components can be mixed together in any way outside the single-chamber syringe  30  and introduced into a barrel  32  of the single-chamber syringe  30 , or the visually-marking and tactilely-marking components can be separately added to the single-chamber syringe  30  and mixed therein. 
     While not shown, the single-chamber syringe can include a static mixer, preferably substantially disposed within the syringe&#39;s barrel. The static mixer can have one or more static mixing components, e.g., a spiraled baffle or any other substantially non-moving parts appreciated by a person skilled in the art, that can mix one or more components of a marking solution disposed in the single-chamber syringe as the marking solution is distally pushed out of the syringe. The components of the marking solution can be fully or partially mixed by the static mixing components depending on one or more factors, such as size of the single-chamber syringe and composition of the marking solution. 
       FIG. 4  illustrates another embodiment of a delivery device for delivering a marking solution. In this embodiment the device is a double-chamber or dual-chamber syringe  34  having first and second chambers  38 ,  42 . This allows two chemicals to be maintained in separate chambers and only mix when delivered, such by using a piston mechanism disposed between the chambers  38 ,  42  and actuated by movement of the syringe&#39;s plunger  44 . Such a configuration is particularly desirable where the visually and tactilely marking components are configured to be disposed in separate chambers (or barrels, discussed below) and react with one another when mixed or where two chemicals are configured to react with one another to form a substantially solid mass that can be visually and tactilely located. The marking solution disposed in the double-chamber syringe  34  can include a first component  36  disposed in the first chamber  38  and a second component  40  disposed in the second chamber  42 . One of the first and second components  36 ,  40  can include a tactilely-marking component while the other one of the first and second components  36 ,  40  can include a visually-marking component. When the double-chamber syringe&#39;s plunger  44  is distally advanced to eject the contents out of a needle  46  at the distal end  48  of the device, the first and second components  36 ,  40  can partially or fully mix together to be delivered from the needle  46  as at least a partially mixed solution. 
       FIG. 5  illustrates another embodiment of a delivery device for delivering a marking solution to a tissue. In this embodiment, the device is a double-barrel syringe  50  having first and second barrels  52 ,  54  that are not in fluid communication with each other. The first and second barrels  52 ,  54  can include first and second solutions  56 ,  58  disposed respectively therein that can mix together when expunged from the double-barrel syringe  50 , e.g., when the syringe&#39;s plunger  60  is distally advanced and the first and second solutions exit out of the syringe&#39;s needle. Although a single plunger  60  is illustrated, each of the barrels  52 ,  54  can include independent plungers and/or plungers configured to be coupled or de-coupled. One of the first and second solutions  56 ,  58  can include a tactilely-marking component while the other one of the first and second solutions  56 ,  58  can include a visually-marking component. The first and second barrels  52 ,  54  can have substantially the same or different volume, and substantially equal or different volumes of the first and second solutions  56 ,  58  (partially or fully filling their respective barrels  52 ,  54 ) can be disposed in the double-barrel syringe  50 . 
       FIG. 6  illustrates still another embodiment of a delivery device in the form of a double-barrel syringe  62  having a mixing chamber  64 , which can optionally include a static mixer. Similar to the double-barrel syringe  50  of  FIG. 5 , the double-barrel syringe  62  includes first and second barrels  66 ,  68  that can respectively have disposed therein first and second solutions  70 ,  72 , one of which can include a tactilely-marking component while the other can include a visually-marking component. Alternatively, the barrels  66 , 68  can each include a chemical configured to react when mixed to form a visual and tactile marking. Distally advancing the syringe&#39;s plunger  74  can puncture or otherwise release a cap or a seal disposed between the barrels  66 , 68  and the mixing chamber  64  and push the first and second solutions  70 ,  72  into the mixing chamber  64  where the first and second solutions  70 ,  72  can at least partially mix before the first and second solutions  70 ,  72  are pushed out a needle  76  at the device&#39;s distal end  78 . Although a single plunger  74  is illustrated, each of the barrels  66 ,  68  can include independent plungers and/or plungers configured to be coupled or de-coupled. The first and second barrels  66 ,  68  can have substantially the same or different volume, and substantially equal or different volumes of the first and second solutions  70 ,  72  (partially or fully filling their respective barrels  66 ,  68 ) can be disposed in the double-barrel syringe  62 . 
     A person skilled in the art will appreciate that other delivery devices can be used to deliver the marking solution to tissue, and that the delivery device can vary in any number of ways from the delivery devices illustrated by way of non-limiting example in  FIGS. 3-6 . For example, a delivery device can include any number of chambers, include any number of barrels, have any number of plungers or other triggering mechanisms, etc. Furthermore, a delivery device can inject a marking solution onto and/or into tissue using a needle, through jet injection, or in any other way appreciated by a person skilled in the art. 
     The needle used to inject a marking solution can have any gauge and various configurations. For example,  FIGS. 7 and 8  illustrate a retractable needle  80 . The needle  80  is disposed within a housing  82  such that in a retracted position, shown in  FIG. 7 , a distal end  84  of the needle  80  is fully contained within the housing  82  and does not extend beyond a distal end  86  of the housing  82 . The needle&#39;s housing  82  can be the shaft of the delivery device, or the housing  82  can be fixedly or removably coupled to a delivery device. The housing  82  can include a visually marking device similar to a tip of a marker or pen configured to apply a visually identifiable surface marking to a tissue when the needle&#39;s distal end  84  is fully contained within the housing  82 . In an extended position, shown in  FIG. 8 , the needle&#39;s distal end  84  can extend a distance L beyond the housing&#39;s distal end  86 . In other words, in the extended position, the needle  80  can penetrate into tissue to a depth equal to the distance L, thereby helping to ensure a desired marking depth and/or to ensure that the needle  80  does not puncture too far into or through a tissue, such as through a body lumen wall. The needle  80  can also be used to puncture through a tissue surface and/or to merely deliver a marking onto, rather than into, a tissue surface. The distance L vary, and it can be a controlled or variable value. For example, actuating a triggering mechanism of the delivery device can controllably advance the needle  80  a predetermined distance L beyond the housing&#39;s distal end  86 , e.g., by pushing a button. Alternatively, actuating the triggering mechanism in varying degrees can advance the needle  80  any variable distance up, e.g., by depressing a plunger. 
     The needle  80  is preferably introduced into a body in the retracted position, thereby helping to prevent the needle  80  from puncturing, snagging, or otherwise contacting tissue or other foreign elements while being introduced into a body and placed in a desirable injection location. Furthermore, the distal end  86  of the housing  82  can be open or it can include a covering  88  disposed over the housing&#39;s distal end  90 . The covering  88  can provide a barrier between the needle  80  and the surrounding environment, e.g., a body cavity, air outside a body, etc. The needle&#39;s distal end  84  can puncture, push through, or otherwise move the covering  88  and become exposed to the external environment when moved from the retracted position to the extended position. 
     The needle  80  can have an angled tip  92  as shown, however, the needle  80  (or any other delivery device needle) can have any shaped tip. For example, as shown in  FIG. 9 , a needle  94  can have a pointed tip  96 . The pointed tip  96  can be substantially conical with a pointed or rounded distal end  98 . In another embodiment, as shown in  FIG. 10 , a needle  100  can have a rounded tip  102 . 
       FIG. 11  illustrates another exemplary embodiment of a delivery device  104  that can apply a marking solution onto tissue. As shown, the delivery device  104  has an elongate shaft  106  with a distal tip  108 . The elongate shaft  106  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  106  is disposed through an introducer, e.g., a cannula or a trocar  110 , having a working channel that extends into a body cavity. The elongate shaft  106  can also include one or more lumens formed therein and extending between proximal and distal ends thereof. The lumen(s) can be used to deliver a marking solution to the distal tip  108 . The distal tip  108  can also have a variety of configurations. In the illustrated embodiment, the distal tip  108  has a nozzle formed thereon for spraying the marking solution onto a tissue surface. In other embodiments, the distal tip  108  can include a brush for brushing the marking solution onto a tissue surface. Again, the particular configuration can vary depending on the intended use. 
     In use, the delivery device  104  can be inserted through the trocar  110 , which is disposed through a tissue surface and into the abdominal cavity (or any other body cavity). As mentioned above, endoscopes or other introducer devices can also optionally be used, and/or the delivery device  104  can be an introducer device that is introduced directly through a natural orifice or through a man-made orifice. Once positioned adjacent to the target tissue, the delivery device  104  can be manipulated using, for example, controls to articulate the distal end of the delivery device  104  and/or controls to actuate the nozzle to deliver the marking solution to tissue. 
     A person skilled in the art will appreciate that a variety of other delivery 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 Sep. 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. 
     A marking solution and/or a delivery device can be disposed within an introducer device at any point before or after the introducer device has been introduced into a body, including before or after the introducer device has been positioned at a desired position proximate to the target tissue. Preferably, the marking solution and/or delivery device is advanced through the introducer device&#39;s working channel after the tissue to be marked has been identified. Although, in some embodiments, the delivery device and/or the marking solution can be pre-loaded into the introducer device. Similarly, the marking solution can be disposed in the delivery device at any point before or after the delivery device has been advanced through the introducer device&#39;s working channel. 
     As illustrated in  FIG. 12 , once the marking solution  22  has been delivered to the tissue  20 , the marker can remain on or in the tissue  20  proximate to the tissue growth  18  after any devices, such as the introducer device  14  and the delivery device  10 , have been removed from the body. As mentioned above, the marker can be palpably and/or visually located on the tissue  20  to help locate the tissue growth  18 . The marker can be configured to be palpably identified (e.g., located by touch) on the tissue  20 , for example by touching the tissue surface  16  in which the marking solution has been injected, thus allowing the location of the tissue growth  18  to be determined. The marker can also be configured to be visually identified on the tissue  20 . Visual observation of the marker can include observing the marker, observing one or more ridges along the tissue&#39;s surface  16 , viewing still or moving images obtained by a scoping device, viewing an x-ray, viewing a barium image, viewing interaction with magnetic particles (if the marking solution  22  includes a magnetized component), tracing radiopharmaceuticals, etc. A person skilled in the art will appreciate that, as mentioned above, visual and/or palpable identification of the marker on the tissue  20  can include visual and/or palpable identification of the marker on or through the tissue&#39;s surface  16 . A person skilled in the art will also appreciate that the marking solution  22  can be doped to be visible in multiple image modalities with a paramagnetic contrast agent such as ferric chloride, ferric ammonium citrate, and gadolinium-DTPA (with and without mannitol) for MRI applications, a short T1-relaxation agent such as mineral oil, oil emulsions, and sucrose polyester for MRI applications, a diamagnetic contrast agent for MRI applications, a superparamagnetic contrast agent such as magnetite albumin microspheres, oral magnetic particles, and superparamagnetic iron oxide (such as manufactured by AMAG Pharmaceuticals, Inc., Cambridge, Mass.) for MRI applications, a perfluorochemical for MRI applications, air aspiration to create bubbles for ultra-sound, and these or any other contrast agents alone or in combination for these or other applications, e.g., CT, PET, fluoroscopy, etc. 
     As previously indicated, the marking solution  22  can mark the tissue  20  proximate to the tissue growth  18  desired for marking, which includes a location where the marking solution  22  directly contacts the desired tissue  18  and/or a location where the marking solution  22  contacts the tissue  20  at a location adjacent to the tissue growth  18 . As illustrated in  FIG. 12 , the marking solution  22  marks the tissue  20  at a shortest distance D from the tissue growth  18 . The distance D can be zero or have any positive value, although the distance D is preferably of a value small enough such that any incision into or any examination of the tissue  20  at the location of the marker allows for relatively easy identification of the tissue growth  18 . Once the marking solution  22  has been delivered proximate to the tissue growth  18 , the distance D remains substantially unchanged until the marker begins bioabsorption or is bioabsorbed by the body, the marker is removed from the body, or the tissue growth  18  is removed from the body. In other words, the marker&#39;s position can be substantially static once the marker is delivered to the tissue  20 . In this way, the marker can remain proximate to the tissue growth  18  and accurately mark the location of the tissue growth  18 . 
     The marker can remain on the tissue  20  for any length of time, e.g., twenty-four hours, two days, one week, two weeks, one month, etc. Being safe for use in the body, the marker could remain on the tissue  20  indefinitely, but preferably, the marker is bioabsorbed after it has been used to locate the tissue growth  18 . The length of time the marker remains on the tissue  20  can depend on any number of factors, such as the marker&#39;s material composition. 
     As shown in another embodiment of marker placement in  FIG. 13 , a distance between a marker  11  and a tissue growth  13  is zero with the marker  11  directly contacting the tissue growth  13 . Here, the tissue growth  13  is formed within a body lumen  15 . The marker  11  can also contact a n inner surface of the body lumen  15  proximate to the tissue growth  13 .  FIG. 13  also illustrates a delivery device  17  that is advanced through a working channel  19  of an introducer device  21  (e.g., a colonoscope) to deliver the marker  11  to the body lumen  15 . The introducer device  21  and the delivery device  17  can be removed from the body lumen  15  (together or separately) after the marker is delivered, and the marker  11  can be palpably identified in the body lumen  15 , as shown in  FIG. 14 , to help locate the desired tissue  13 . The marker  11  can be palpably located directly, or the marker  11  can be palpably located through one or more layers of tissue adjacent to the body lumen  15 , e.g., from outside a patient&#39;s body. As discussed above, the marker  11  can also or instead be visually located. 
     As mentioned above, when used in the body, light or other energy may need to be delivered to a tissue containing a marker to enable visual identification of the marker to locate the target tissue. The energy source can be external to the body for delivering energy internally, or an internal energy source can be used for internal application. Exemplary energy application methods and devices are described in U.S. application Ser. No. 11/771,490 of Voegele et al. filed Jun. 28, 2007 and entitled “Nanoparticle Tissue Based Identification and Illumination,” mentioned above. In an exemplary embodiment, electromagnetic energy can be delivered to fluorescent nanoparticles disposed within a patient&#39;s body using a delivery apparatus, such as an endoscope or laparoscope. The delivery apparatus can be located externally, e.g., above a 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. 
     In an exemplary embodiment, the energy source is light, i.e., electromagnetic radiation, and the reading apparatus has an elongate shaft configured to be inserted into a body lumen and including 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. 15  illustrates one exemplary embodiment of a laparoscope  112  that has two illumination or light emitting sources, generically illustrated as elements  114 A,  114 B. As shown, the laparoscope  112  utilizes an optical switch  116  to select the illumination source(s). One illumination source can 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 can 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  116  can connect the selected source  114 A,  114 B to an optical fiber bundle (not shown) that extends through the laparoscope  112  for transmitting the light through an eyepiece at the distal end of the laparoscope  112 . When the light is transmitted, e.g., by depressing a switch, button, or foot pedal, generically illustrated as element  118 , the fluorescent nanoparticles on the tissue will excite and fluoresce. The laparoscope  112  can also include an image receiving apparatus or camera  120  for collecting the reflected light from the fluorescent nanoparticles, and a filter switch  122  to place the appropriate optical filter between the eyepiece and the camera  120 . The filter that is used for visualization of the nanoparticles, for example, must be highly efficient at rejecting the excitation wavelength in order to avoid saturation of the camera  120  while still being highly transparent at the wavelength of the emission of the nanoparticles. 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. 15 , the captured image can be transmitted to a monitor  124  coupled to the camera  120  by a camera control box  126 . The monitor  124  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  112  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. 
     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 can 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 can be an independent source that couples to the instrument. 
     The devices disclosed herein can be designed to be disposed of after a single use, or they can be designed to be used multiple times. In either case, however, the device can be reconditioned for reuse after at least one use. Reconditioning can include any combination of the steps of disassembly of the device, followed by cleaning or replacement of particular pieces, and subsequent reassembly. In particular, the device can be disassembled, and any number of the particular pieces or parts of the device can be selectively replaced or removed in any combination. Upon cleaning and/or replacement of particular parts, the device can be reassembled for subsequent use either at a reconditioning facility, or by a surgical team immediately prior to a surgical procedure. Those skilled in the art will appreciate that reconditioning of a device can utilize a variety of techniques for disassembly, cleaning/replacement, and reassembly. Use of such techniques, and the resulting reconditioned device, are all within the scope of the present application. 
     Preferably, the invention described herein will be processed before surgery. First, a new or used instrument is obtained and if necessary cleaned. The instrument can then be sterilized. In one sterilization technique, the instrument is placed in a closed and sealed container, such as a plastic or TYVEK bag. The container and instrument are then placed in a field of radiation that can penetrate the container, such as gamma radiation, x-rays, or high-energy electrons. The radiation kills bacteria on the instrument and in the container. The sterilized instrument can then be stored in the sterile container. The sealed container keeps the instrument sterile until it is opened in the medical facility. 
     It is preferred that device is sterilized. This can be done by any number of ways known to those skilled in the art including beta or gamma radiation, ethylene oxide, steam, and a liquid bath (e.g., cold soak). 
     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.