Particles with radiation activated adhesive

Techniques are generally described for particles with a surface including an adhesion material. The adhesion material may be selectively activated in response to radiation. The particles may be distributed proximate to a target through a fluid system. Radiation may be emitted toward the target causing the adhesion material to activate. The activated adhesive material on the surface of the particles may adhere to the target providing a fiducial mark or reference point. The fiducial mark may be visible through a medical imaging technique. In some examples, the particles may be nanoparticles. In some examples, the radiation may be infrared radiation.

BACKGROUND

Nanoparticles may be used for applying photo-thermal therapy to treat various medical conditions. For instance, gold nanoparticles, in combination with infrared radiation, may be used to apply photothermal therapy to a localized area, such as an organ of a human subject. In particular, gold nanoparticles may be distributed through a subject's body. Infrared radiation may then be projected on the subject's body at the localized area. Gold nanoparticles exposed to the radiation convert the radiation to heat, providing thermal therapy to the localized area of the subject.

DETAILED DESCRIPTION

The following detailed description, reference is made to the accompanying drawings, which form a part hereof. In the drawings, similar symbols typically identify similar components, unless context dictates otherwise. The illustrative examples described in the detailed description, drawings, and claims are not meant to be limiting. Other examples may be utilized, and other changes may be made, without departing from the spirit or scope of the subject matter presented herein. It will be readily understood that the aspects of the present disclosure, as generally described herein, and illustrated in the Figures, may be arranged, substituted, combined, separated, and designed in a wide variety of different configurations, all of which are implicitly contemplated herein.

This disclosure is drawn, inter alia, to methods, systems, devices, and/or apparatus generally related to particles comprising a radiation activated adhesive on a surface thereof.

Some example devices and methods may utilize techniques described herein to adhere at least a portion of a plurality of particles to a target. In some examples, a plurality of particles may be distributed through a fluid system proximate to a target. A radiation source may be configured to emit radiation on the particles proximate the target to activate the adhesive on the surface of the particles. Once the adhesive on the surface of the particles has been activated, at least some of the particles may adhere to the target. The plurality of particles may be configured to be visible through medical imaging using any of a variety of techniques. In some examples, the particles are nanoparticles. In some examples, the target may be in a live subject. For instance, the target may be a lumen, such as sidewalls of a blood vessel, in and/or on an organ, a tissue, a tumor, or the like within a body of the live subject. In some examples, the adhered particles may be visible under a medical imaging technique. In many examples, the particles may be provided to the live subject intravenously and distributed to the target through blood circulation.

FIG. 1is a schematic illustration of a system100adapted to mark a target in accordance with at least some examples of the present disclosure. The example system100may include a particle source108, a plurality of particles110, a target112, and a radiation source, such as a radiation illuminator114. Although not illustrated inFIG. 1, the target112may be located in a subject, such as a human body or other live subject. In some examples, the target112may be a lumen in and/or on a tissue, an organ, a tumor, and/or some other body structure in the live subject.

The particles110, which include adhesion material, may be distributed proximate to the target112. In some examples, the particles may be distributed proximate to the target via a fluid system106. The fluid system106may comprise a liquid or a gas. The radiation illuminator114may be adapted to selectively and/or contiguously emit radiation116toward the target112. The radiation illuminator114may be configured to emit any type of radiation, such as infrared, radio waves, visible light, ultraviolet light, ultrasound, etc. The radiation illuminator114emits radiation on a region120. The adhesion material in at least some of the particles110in the region120that are proximate to the target are activated in response to the radiation emitted from the radiation illuminator114. Once the adhesive material is activated, at least some of the particles110that are proximate to the target112may adhere to the target112.

The example system may further include a filter124configured to block some of the radiation116being emitted from the radiation illuminator114. In particular, the radiation illuminator114may be configured to emit two kinds of radiation, such as near-infrared and visible radiation. The filter124may be configured to block the visible radiation116a, but allow the near-infrared radiation116bthrough the filter124.

The particles110that are adhered to the target may be used as a fiducial mark. Various medical imaging techniques, which will be further discussed below, may be used to evaluate and/or track any changes associated with the target. For example, the fiducial mark may be an initial reference point that identifies a specific location and/or orientation associated with the target112, such as might be used as a baseline for evaluating a medical condition. Further medical images may be taken at a later time, or under some other condition such as when a patient undergoes a physical stress or trauma. The medical images can be compared to identify changes in the position and/or orientation associated with the target based on the fiducial mark changing from the reference point to another point.

A processor118may be coupled to the radiation illuminator114. The processor118may be configured to cause the radiation illuminator114to selectively emit radiation166toward the target112. The amount of radiation emitted from the radiation illuminator114may vary and the time duration of emitting the radiation116may vary. In one example, the processor118may be configured to control the amount of energy and/or the duration that the radiation116is emitted from the radiation illuminator114. For instance, in some examples, the time duration may be contiguous at a particular radiation level or pulsed over an elapsed time. The width of the pulse may be constant, varying, or a combination thereof. The processor118may be further configured to control the total radiation exposure time limit and/or energy level.

A movement sensor122may be coupled to the radiation illuminator114and/or the processor118. The movement sensor122may be configured to detect movement in the target112. As will be explained in more detail below, the radiation illuminator114may emit radiation116when the target112is still and stop emitting radiation when the target112moves. For instance, the movement sensor122may be configured to detect movement in the target112and transmits a movement signal to the processor118. Responsive to the movement signal, the processor may transmit a signal to the radiation illuminator114that causes the radiation illuminator114to stop emitting radiation. Alternatively, the movement sensor122may be an imaging device, such as a camera or magnetic resonance imaging (MRI) configured to detect motion in the target.

In some examples, the particles110may be any particle having dimensions that are less than about 1 centimeter. For instance, in some examples, the particles are nanoparticles, microparticles, miliparticles or any combination thereof. The particles110may be at least partially coated in a radiation activated adhesive material. That is, the adhesive material may remain inactive until it is exposed to the radiation116. The radiation116may activate the adhesive material directly, indirectly or a combination thereof. In the case of directly activating the adhesive material, the radiation directly interacts with the adhesive material to activate the adhesive properties. In some examples, the adhesive material may be directly activated by thermal energy that is sourced from the radiation. Alternatively, in the case of indirectly activating the adhesive material, the radiation116may thermally activate the adhesive by heating the particle110or nanoparticles, which in turn causes the adhesive properties of the adhesive material to be activated. In this example, the adhesive may remain inactive on the nanoparticles until it is thermally activated. In some examples, the radiation116may also activate a thermally activated adhesive material by heating both the nanoparticle and the adhesive material.

The particle may be fabricated to form the adhesive material as a byproduct of the fabrication process of the particle itself. Alternatively, one or more layers of the adhesive material may be applied to an outer surface of the particle110after the particle is manufactured. In some examples, the adhesive is a bio-compatible material and/or a polymer material, such as poly-anhydrides-co-imides or other polymer materials.

FIG. 2is a schematic illustration of particles, such as nanoparticles210, circulating in the bloodstream216of a human subject208in accordance with at least some examples of the present disclosure. The nanoparticles210may be provided to the bloodstream216of the human subject208intravenously. The bloodstream216may circulate the nanoparticles210through the body of the subject208such that the nanoparticles210enter various body structures, such as cells, tissues, organs, glands, tumors, or the like. Example body structures may include blood, liver, spleen, kidney, testis, thymus, heart, lung, brain, etc. The radiation illuminator114ofFIG. 1may be configured to project infrared radiation116through the skin of the live subject208to an intended target. For instance, if the intended target is sidewalls of a blood vessel in and/or on a lung218of a subject208, the radiation illuminator114may be arranged to emit infrared radiation through the skin of the subject208to the lung218. As discussed above, the infrared radiation116from the radiation illuminator114will activate the adhesive material for those nanoparticles210that are within range of the infrared radiation116. Therefore, at least some portion of those nanoparticles210having the activated adhesive material that are proximate to the lung may adhere to sidewalls of a blood vessels in and/or on the lung218. The adhesive bond may be a chemical bond, a mechanical bond, or a hydrogen bond.

The nanoparticles210that adhere to the lumen or sidewalls of a blood vessel in and/or on the organ to form a fiducial mark that may act as a body reference point and may provide orientation and location to a medical professional. For example, a fiducial mark on the liver may be used to guide a beam during non-invasive treatments or surgery. The fiducial mark may be used as a mark for receiving the beam. Alternatively, the mark may be a reference point to orient and guide the medical professional within the body. The nanoparticles210that adhere to the lumens in and/or on the organ and form the fiducial mark may be visible under imaging systems such as X-ray, magnetic resonance imaging (MRI), or other methods. Once the fiducial mark has been formed (i.e., by activation of the adhesion material), the remaining nanoparticles210in the bloodstream216may be removed from the bloodstream216.

Various body structures, such as the liver or the lung, may receive higher concentrations of nanoparticles210as nanoparticles are distributed through the bloodstream through blood circulation. Therefore, the amount of nanoparticles210distributed to the bloodstream216may be varied depending on the target. For instance, the liver is well known to absorb higher concentration levels of nanoparticles210than the brain. Therefore, if the liver is the determined target, lower levels of concentration of nanoparticles210may be distributed to the bloodstream216than if the brain was the target. Concentration levels may range from an order of thousands of nanoparticles per cubic centimeter to 1 nanoparticle per cubic centimeter or less.

The duration at which the nanoparticles210are distributed to the target may also depend on which body structure is the target. In general, the nanoparticles210may be distributed to the target in manner to prevent the formation of plaque build up or blockages. Therefore, the number of nanoparticles210being distributed and the rate at which the nanoparticles210are distributed to the target may be sufficiently low to prevent such blockages in the bloodstream. For instance, in some examples, the nanoparticles210may be circulated in or distributed to the bloodstream216over a period of hours. In some instance, such as when the target is a lung and is, therefore, a moving target, the nanoparticles may be distributed through the bloodstream for up to 8 hours and in some instance for more than 8 hours. In other examples, the particles may be distributed to the bloodstream for a matter of minutes. The rate at which particles are distributed in the bloodstream may vary depending on the particle size, the target, the injection method of providing the particles into the bloodstream, or any combination thereof.

When used in a live subject, the nanoparticles210and the thermally activated adhesive may be made from biocompatible materials. For instance, in many examples, the thermally activated adhesive may be a biocompatible adhesive, such as poly(anhydride-co-imides). Examples of biocompatible adhesives are well known in the art and are further described in Uhrich et al,Synthesis and Characterization of Degradable Poly(anhydride-co-imides, Macromolecules 28: 2184-93 (1995), hereby incorporated by reference herein in its entirety for any purpose. The nanoparticle may be formed from a material such that once it adheres to the target to form the fiducial mark, the fiducial mark may be visible under imaging systems such as X-ray, magnetic resonance imaging (MRI), or other methods. Furthermore, the nanoparticles210may be a material that does not interfere with some medical imaging techniques such as X-rays, MRIs, gamma knife, and other medical methods. In some examples, the nanoparticles210may be gold, gadolinium, or a combination thereof. In other examples, the nanoparticles210may be other gold or gadolinium alloys. In yet other examples, the nanoparticles210may be other metals, glass, plastic, or a particle of some other type of material. In other examples, the nanoparticle is the adhesive material itself.

The size of the nanoparticles210may vary depending on the target. For instance, nanoparticles having a maximum dimension of approximately 10 nm or less may easily enter body structures associated with blood, liver, spleen, kidney, testis, thymus, heart, lung, and/or brain. Suitable nanoparticles sizes in relation to bodily distribution has been studied and examples may be found in De Jong et al,Particle Size-dependent Organ Distribution of Gold Nanoparticles After Intravenous Administration, Biomaterials Volume 29, Issue 12, April 2008, pages 1912-1919, hereby incorporated by reference in its entirety for any purpose. The nanoparticle may have a maximum dimension larger than approximately 10−9meters. In some instance, the nanoparticles may have a maximum dimension between 1 nm and 100 nm. In some examples, the maximum dimension may be a length for a rod shaped nanoparticle or a diameter for a sphere shaped particle.

As indicated above with reference toFIG. 1, a filter that prevents transmission of radiation other than an intended radiation, such as infrared radiation, may be used. For instance, a filter may be used to prevent visible light from being emitting. This may assist in preventing heat from being applied to the surface of the subject's skin, causing discomfort to a live subject. Other types of radiation may also be filtered as may be desired in a particular example implementation. For instance, x-rays or radio wave radiation may be filtered out in some example systems.

In some examples, the infrared radiation may compensate for biological activity of the live subject. For instance, the infrared radiation may be projected in a manner that coincides with the movement of a biological target, such as the movement of an organ. In some examples, the infrared radiation may be provided intermittently to accommodate biological movement of the target via a processor (such as that described inFIG. 1) that is adapted in accordance with various methods or processes that turn on and off the radiation illuminator or other radiation energy source. For instance, assuming the target is a human lung, as the subject breathes, the precise location of the target may vary. A movement sensor, such as the movement sensor122inFIG. 1, may be adapted to detect when the lung is expanded. Therefore, the system may adaptively control the infrared illuminator such that infrared radiation is emitted towards the lung (the target) while the lung is expanded and infrared radiation is not emitted towards the lung when the lung is contracted.

The infrared radiation may be projected at low levels over an extended period of time sufficient to prevent the formation of plaque or blockages. For instance, a small number of nanoparticles may be selectively activated at a particular time so that the total number of nanoparticles activated at that particular time does not result in the formation of a hazardous blockage. In some examples, the infrared radiation may be near-infrared radiation. Once the target site has been sufficiently marked, the remaining nanoparticles may be flushed out of the body. In some examples, the fiducial mark may remain on the target for extended time periods, thus facilitating long-term diagnostic observations and comparisons. That is, the fiducial mark may be used to track morphological changes in the live subject that may occur overtime or when subject to a physical stress or other condition. For example, the fiducial mark may be used to track enlargement or shrinkage of an organ or a tumor over time. This may be used to facilitate calculating a rate at which a tumor, organ, or other internal features grow or shrink.

FIG. 3is a schematic illustration300of nanoparticles310adhering to a target in a human subject308in accordance with at least some examples of the present disclosure. The schematic illustration300may be representative of an MRI image. The target in this example is a lung312. As is illustrated inFIG. 3, the nanoparticles310may adhere to the lung312to form a fiducial mark306. The fiducial mark306in this example is a circle with an X-shaped mark formed therein (although any other appropriate/desired shape can be utilized). The fiducial mark306may move with the lung312as the lung312expands and contracts. The fiducial mark306may be used to track morphological changes in the lung312over long periods of time. For instance, the fiducial mark306may be used to track the size of the lung312over time to detect growth, shrinkage, or some other phenomena that may cause movement of the position and/or alignment of the fiducial mark306.

The fiducial mark306may be used as a guide or reference point during non-invasive treatment. In some examples, the fiducial mark306may be visible under imaging techniques such as X-ray, MRI, or the like. Furthermore, in many examples, the fiducial mark may not be disruptive during such imaging. In one example, the fiducial mark306may first be characterized with a detailed imaging system such as MRI. Then the fiducial mark306may be used to guide beams, such as particle beams, or other therapy using an X-ray image. The fiducial mark306may provide an internal reference point that may orient a medical practitioner. In some examples, characterizing the fiducial mark306may further include generating a 3D model of internal portions of the human body including the fiducial mark306. The various methods and/or processes for assisting the medical practitioner using the fiducial mark306may be either manual or automated. For automated methods and/or processes, a computing device or other similar processor based systems may be arranged to monitor/key off of the fiducial mark306.

FIG. 4is a schematic illustration of a system400for imaging a fiducial mark410on a target412in accordance with at least some examples of the present disclosure. The example system400may include an imaging source416adapted to provide an image of at least a portion of the target412and the fiducial mark410. In particular, the image source416may include an effective area414that may be aligned with at least a portion of the fiducial mark410on the target112. The imaging source416may be any medical imaging device being used now or in the future that is adapted to provide an image of the fiducial mark and target, such as an MRI or X-ray device. The example system400may include a processor418, a movement sensor420, and/or a memory422. The processor418may be coupled to the imaging source416and may be configured to control the amount of energy emitted from the imaging source416. The movement sensor420may be coupled to the processor418and/or the imaging source416. The movement sensor420may be adapted to sense movement of the fiducial mark410on the target412. The processor418may be adapted to adjust the amount of energy emitted from the imaging source in response to movement sensed by the movement sensor420. A memory422may be coupled to the processor418and configured to store the data image. The memory422may be further configured to store a reference image of the target412itself or the target412and fiducial mark410taken previously. The memory422may be further configured to store settings for imaging the fiducial mark410, such as power level of the imaging source, duration of exposure, total amount of energy transmitted, etc.

FIG. 5is a schematic illustration of a system500adapted to mark a target512in accordance with at least some examples of the present disclosure. At least some of the components in the system500may be used in the system100fromFIG. 1. For instance, the example system500may include a particle source108, particles110, a filter124, etc. as is illustrated inFIG. 1. The example system500may include a target512, a reflective device520, and a radiation illuminator514. The reflective device520may be arranged to reflect the radiation emitted from the radiation illuminator514onto the target512. The reflective device520may comprise reflective components arranged in an intended pattern. The reflective device520may be arranged to receive the radiation from the radiation illuminator514and reflect the radiation in the form of the pattern onto the intended target512. Thus, the fiducial mark may take the form of the pattern on the reflective device520. The reflective device520in the example system500may be a micro-mirror array. However, other reflective devices500may be used, such as, for example, a transmissive LCD imager. The intended pattern may take any form or shape. In some examples, the intended pattern is an X-shaped mark, a plus-shaped mark (e.g., +), a cross-hairs-shaped mark (e.g.,), a square-shaped mark (e.g., □), a circular or oval-shaped mark, any other shaped mark, or combination thereof. In these examples, the fiducial mark may take the shape of the emitted pattern. The fiducial mark may provide not only position but also orientation (e.g., rotational orientation, possibly an orientation in multiple dimensions). In other examples, the reflective device520may be a dynamic reflective device, such as a digital mirror device. In this example, a sensor, such as a movement sensor, detects movement in the target, the pattern of the fiducial mark may change shape, such as from an X fiducial mark to a square fiducial mark. Thus, the fiducial mark may be dynamic and thus modified in response to movement of the target.

FIG. 6is a flow chart illustrating an example method600of adhering nanoparticles to a target in accordance with at least some examples of the present disclosure. The method600may include one or more functions, operations, or actions as illustrated by blocks610and/or620. The example method may begin at block610. In block610, a plurality of particles may be provided proximate to a target. Block610may be followed by block620. In block620, radiation may be emitted toward the target (e.g., by a radiation source) to thermally activate adhesive material on the surface of the plurality of particles that are proximate to the target thereby causing at least some of the particles to adhere to the target. The method600may be performed in an order or combination other than is illustrated and may include steps not shown. For instance, radiation may be emitted toward the target before, after, or while the plurality of particles are being provided proximate a target.

As generally described above (see discussion ofFIGS. 1 and 2), the nanoparticles may be distributed sufficiently proximate the target to adhere to the target once the adhesive is thermally activated. In some examples, the target is within a body of a live subject. In these examples, the infrared radiation (or some other variety of radiation) may be emitted through the skin of the live subject to the target site. The amount of infrared radiation may be controlled (e.g., via a computing device) to prevent the formation of plaque and blockages. In some examples, a low level of infrared radiation is used over a long period of time.

FIG. 7is a flow chart illustrating an example method of emitting radiation toward a moving target in accordance with at least some examples of the present disclosure. The method700may include one or more functions, operations, or actions as illustrated by blocks710,720, and/or730. The example method may begin at block710. In block710, an exposure profile may be set for the target. The exposure profile may include a variety of parameters, such as an energy level associated with a radiation source, a time or duration for exposure at a particular energy level, a period or pulse width for exposing at a particular energy level, a total radiation exposure time, a total energy exposure level, or the like, or any combination thereof. Block710may be followed by block720. In block720, movement of the target may be monitored. Block720may be followed by block730. In block730, the radiation source may be selectively activated when the target is not moving. For instance, the radiation source may activate at set levels and times when the patient is not moving. Once one or more parameters in the exposure profile are met, the process may be terminated. For instance, in one example method, the process is terminated when the radiation energy limit is reached or when the total exposure time has expired. The method700may be performed in an order or combination other than is illustrated and may include additional blocks not shown.

FIG. 8is a block diagram illustrating an example computing device900that may be arranged for adapting to mark a target and/or imaging a target in accordance with at least some examples of the present disclosure. In a very basic configuration901, computing device900typically may include one or more processors910and system memory920. A memory bus930may be used for communicating between the processor910and the system memory920.

Depending on the desired configuration, processor910may be of any type including but not limited to a microprocessor (μP), a microcontroller (μC), a digital signal processor (DSP), or any combination thereof. Processor910may include one or more levels of caching, such as a level one cache911and a level two cache912, a processor core913, and registers914. An example processor core913may include an arithmetic logic unit (ALU), a floating point unit (FPU), a digital signal processing core (DSP Core), or any combination thereof. An example memory controller915may also be used with the processor910, or in some implementations, the memory controller915may be an internal part of the processor910.

Depending on the desired configuration, the system memory920may be of any type including but not limited to volatile memory (such as RAM), non-volatile memory (such as ROM, flash memory, etc.) or any combination thereof. System memory920may include an operating system921, one or more applications922, and program data924. Application922may include a radiation emitting application923that may be arranged to generate an exposure profile for an intended subject and monitor movement and exposure to the subject. The application may be configured to receive signals indicative of movement of the intended target, signals indicative of when a radiation source has reached a particular energy level, signals relating to the time and/or duration of radiation emitted. The application may be further configured to generate signals to cause the radiation source to pulse or set exposure times. Program Data924may include types of targets and radiation energy levels associated with particular targets925that is useful for determining the appropriate energy level for an intended target, as will be further described below. In some embodiments, application922may be arranged to operate with program data924on an operating system921in accordance with one or more of the techniques, methods, and/or processes described herein. This described basic configuration is illustrated inFIG. 9by those components within dashed line901.

Computing device900may have additional features or functionality, and additional interfaces to facilitate communications between the basic configuration901and any required devices and interfaces. For example, a bus/interface controller940may be used to facilitate communications between the basic configuration901and one or more data storage devices950via a storage interface bus941. The data storage devices950may be removable storage devices951, non-removable storage devices952, or a combination thereof. Examples of removable storage and non-removable storage devices include magnetic disk devices such as flexible disk drives and hard-disk drives (HDD), optical disk drives such as compact disk (CD) drives or digital versatile disk (DVD) drives, solid state drives (SSD), and tape drives to name a few. Example computer storage media may include volatile and nonvolatile, removable and non-removable media implemented in any method or technology for storage of information, such as computer readable instructions, data structures, program modules, or other data.

Computing device900may also include an interface bus942for facilitating communication from various interface devices (e.g., output interfaces, peripheral interfaces, and communication interfaces) to the basic configuration901via the bus/interface controller940. Example output devices960include a graphics processing unit961and an audio processing unit962, which may be configured to communicate to various external devices such as a display or speakers via one or more A/V ports963. Example peripheral interfaces970include a serial interface controller971or a parallel interface controller972, which may be configured to communicate with external devices such as input devices (e.g., keyboard, mouse, pen, voice input device, touch input device, etc.) or other peripheral devices (e.g., printer, scanner, etc.) via one or more I/O ports973. An example communication device980includes a network controller981, which may be arranged to facilitate communications with one or more other computing devices990over a network communication link via one or more communication ports982.

While various aspects and examples have been disclosed herein, other aspects and examples will be apparent to those skilled in the art. The various aspects and examples disclosed herein are for purposes of illustration and are not intended to be limiting, with the true scope and spirit being indicated by the following claims.