WO2014159585A1

WO2014159585A1 - Systems and methods for monitoring fluid flow in shunt systems and other flow-related conduits

Info

Publication number: WO2014159585A1
Application number: PCT/US2014/024295
Authority: WO
Inventors: Eric Leuthardt; David Limbrick; Phil BAYLY; Guy Genin; Matt Reynolds; Brent YTTERBERG; Sean ERMER; Lihong Wang; Matt SMYTH; Dan Moran; Srikanth Singamaneni
Original assignee: Washington University
Priority date: 2013-03-14
Filing date: 2014-03-12
Publication date: 2014-10-02

Abstract

A flow monitoring apparatus includes at least one conduit configured to couple to the flow conduit system, the at least one conduit defining a channel for a fluid flow. A material exhibiting a strain-sensitive Raman scattering signal positioned within the channel, wherein at least a portion of the material is configured to deform when the fluid flows through the channel. A light source is configured to direct light onto the material to generate a spectroscopic signal to detect deformation of the material. The identification of the deformation allows a user to determine a flow rate of the fluid.

Description

SYSTEMS AND METHODS FOR MONITORING FLUID FLOW IN

SHUNT SYSTEMS AND OTHER FLOW-RELATED CONDUITS

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Patent Application No. 61/782, 127 filed on March 14, 2013, which is hereby incorporated by reference in its entirety.

BACKGROUND

[0002] The field of the invention relates generally to monitoring systems that are configured to monitor fluid flow in shunt systems and flow-related conduits and, more particularly, to a flow monitoring apparatus that may be used with such monitoring systems.

[0003] Approximately 75,000 people per year suffer from an accumulation of cerebrospinal fluid (CSF) within the ventricles in the brain. Such a condition is also known as hydrocephalus. Moreover, approximately 1 in 500 children are born with hydrocephalus. While there is no known cure for hydrocephalus, the condition is commonly treated with a shunt system, such as a ventriculoperitoneal shunt system, which facilitates the flow of CSF from the ventricles of the brain to the peritoneal cavity.

[0004] Such known shunt systems may include a valve to control the flow of CSF and a catheter that is coupled to either end of the valve. The valve may be placed on top of the skull, under the scalp, during surgery and the proximal end of the catheter is inserted into the ventricle of the brain. The distal end of the catheter is routed subcutaneously into the peritoneal cavity (or occasionally the right atrium of the heart). The valve regulates fluid flow to maintain a healthy intracranial pressure. The entire system remains in place underneath the skin unless a complication occurs.

[0005] At least some known shunt systems are prone to frequent failure. For example, protein may build up at the distal and proximal ends of the catheter resulting in a blockage that may cause damage to the shunt system. Valve malfunctions and over drainage of the brain can also cause damage to the shunt system. A failed shunt system may be life threatening to the patient or may cause permanent brain damage.

[0006] As such, it is imperative to determine whether the shunt system is operating appropriately. However, a failed shunt system cannot be readily identified by a healthcare professional. For example, early symptoms of a malfunctioning shunt may include symptoms, such as headaches and nausea. Such symptoms may be over looked as being related to a failed shunt system and may, instead, be construed as symptoms for other common diseases, such as a cold or a flu. Radioactive isotopes may be used to determine if there is a block in the shunt system. However, using such a technique can be invasive and is not efficient and/or cost effective. For example, using such a technique requires performing brain surgery on the patient, which can be invasive and require machinery. Moreover, such a technique does not measure the actual flow rate within the shunt system.

[0007] Similar flow related problems are also found in other flow conduits in the body such as vascular graft, arteriovenous fistulas, vascular stents, and artificial valves. For each of these flow related devices, there is a critical need to understand how blood is moving through the tubular conduit. As an example, it would be important to know if blood flow is being altered through a vascular graft as it could be indicative of a narrowing of that graft which could portend a vascular obstruction that could be clinically catastrophic and lead to subsequent limb amputations. Similarly, a stent occlusion to a vessel if flow dynamics are altered and detected ahead of occlusion could allow for intervention to prevent potential impairment of flow (and damage) to an end organ such as the heart or brain. Other end organs could include the intrabdominal organs such as the kidney or intestines, or the limbs, such as the arms or legs.

BRIEF DESCRIPTION

[0008] In one aspect, the present disclosure is directed to a flow monitoring apparatus for monitoring fluid flow within a flow conduit system. The flow monitoring apparatus comprises: at least one conduit configured to couple to the flow conduit system, the at least one conduit defining a channel for a fluid flow; a material exhibiting a strain-sensitive Raman scattering signal positioned within the channel, wherein at least a portion of the material is configured to deform when the fluid flows through the channel; and a light source configured to direct light onto the material to generate a spectroscopic signal to detect deformation of the strain-sensitive material.

[0009] In another aspect, the present disclosure is directed to a monitoring system for monitoring fluid flow within a flow conduit system. The monitoring system comprises: a flow monitoring apparatus comprising: at least one conduit configured to couple to the flow conduit system, the at least one conduit defining a channel for a fluid flow; a material exhibiting a strain-sensitive Raman scattering signal positioned within the channel, wherein at least a portion of the material is configured to deform when the fluid flows through the channel; a light source configured to direct light onto the material to generate a spectroscopic signal to detect deformation of the material; and a computing device coupled to the flow monitoring apparatus configured to generate an output of the spectroscopic signal for display to a user to identify whether the material is deformed.

[0010] In another aspect, the present disclosure is directed to a method for monitoring fluid flow within a flow conduit system. The method comprises coupling at least one conduit to the flow conduit system, the at least one conduit defining a channel for fluid flow within the flow conduit system, wherein a material exhibiting a strain-sensitive Raman scattering signal is positioned within the channel and wherein at least a portion of the material deforms when the fluid flows through the channel; directing light from a light source onto the material to generate a spectroscopic signal to detect deformation of the strain-sensitive material; generating an output of the spectroscopic signal, via a computing device; and displaying the output of the spectroscopic signal, via the computing device, to a user. The method for monitoring fluid flow within a flow conduit system can be used, for example, to identify whether the material is deformed. The method for monitoring fluid flow within a flow conduit system can also be used, for example, to identify how much the material is deformed.

BRIEF DESCRIPTION OF THE DRAWINGS

[0011 ] FIG. 1 is an exemplary monitoring system for monitoring fluid flow within a shunt system;

[0012] FIG. 2 is an exploded perspective view of an exemplary flow monitoring apparatus that may be used with the monitoring system shown in FIG. 1 ;

[0013] FIG. 3 is a cross-sectional view of a portion of the flow monitoring apparatus shown in FIG. 2 and taken along line 3-3; and

[0014] FIG. 4 is a graphical output that may be generated by the monitoring system shown in FIG. 1.

[0015] FIG. 5 is a scanning electron microscope image of polymer nanotubes formed by layer-by-layer assembly of polyelectrolytes in a porous alumina membrane.

[0016] FIG. 6 is a schematic illustrating the synthesis of gold nanostars on the surface of graphene oxide. [0017] FIG. 7A is a low magnification transmission electron microscope image of gold nanostars on a graphene oxide surface.

[0018] FIG. 7B is a higher magnification transmission electron electron microscope image of gold nanostars on a graphene oxide surface.

[0019] FIG. 7C is a high magnification transmission electron microscope image of gold nanostars.

[0020] FIG. 7D is an atomic force microscope image of gold nanostars on a graphene oxide surface.

[0021] FIG. 8A is a graph illustrating VIS-NIR extinction spectra showing the tunable surface plasmon resonance band of gold nanostars on a graphene oxide surface by changing the graphene oxide to gold ratio.

[0022] FIG. 8B is a graph illustrating the Raman spectra of gold nanostars, graphene oxide and gold nanostars on a graphene oxide surface electrostatically adsorbed on silicon.

DETAILED DESCRIPTION

[0023] The exemplary systems, apparatus, and methods described herein overcome at least some known disadvantages associated with at least some known monitoring systems that are used to monitor shunt systems and flow-related conduits. More specifically, the embodiments described herein provide a monitoring system that enables a non-invasive and relatively quick approach to measuring the flow rate within a shunt or flow related system to determine whether the system is working appropriately. The monitoring system includes a flow monitoring apparatus and a computing device that is coupled to the flow monitoring apparatus. The flow monitoring apparatus is coupled directly to the shunt or flow related system and uses a light source for performing spectroscopic measurements to determine the flow rate within the system. The computing device is configured to generate an output of the spectroscopic measurements for display to a user to enable the user to determine the flow rate of the fluid within the system. Based on the flow rate, the user can then identify whether the shunt or flow related system is working appropriately. Because the flow monitoring apparatus is coupled directly to the shunt or flow related system, using such a monitoring system enables a non-invasive approach to directly measure the flow rate within the shunt or flow related system. Moreover, healthcare professionals can readily identify any problems with the shunt or flow related system without having to perform any procedures, such as surgical procedures. [0024] FIG. 1 is an exemplary monitoring system 100 that is coupled to a cerebrospinal fluid shunt system 101 implanted in a patient 102. It should be noted that in the exemplary embodiment, shunt system 101 is a ventriculoperitoneal shunt system that facilitates fluid flow, such as cerebrospinal fluid (CSF), from at least one ventricle (not shown) of a brain of patient 102 to a peritoneal cavity 103 of patient 102. While the exemplary embodiment includes a ventriculoperitoneal shunt system, the embodiments of the systems, apparatus, and methods described herein are not limited to any one particular type of shunt system, and one of ordinary skill in the art will appreciate that the systems, apparatus, and methods described herein may be used in connection with other systems. It should also be noted that, as used herein, the term "couple" is not limited to a direct communicative, mechanical, and/or an electrical connection between components, but may also include an indirect communicative, mechanical, and/or electrical connection between multiple components.

[0025] Shunt system 101, in the exemplary embodiment, includes a proximal section 104 and a distal section 106, wherein a catheter 107 is located within proximal section 104. In the exemplary embodiment, at least a portion of catheter 107 is positioned within a fluid filled space within a body, such as a ventricle (not shown) of the brain in a body of patient 102. Fluid filled space may include a ventricle, a cyst, and/or an abscess within the body. In other embodiments, catheter 107 may be positioned in other areas of patient 102 and at least a portion of catheter 107 may be positioned within a ventricle located in other parts of patient 102, such as a heart ventricle.

[0026] Shunt system 101, in the exemplary embodiment, also includes a valve 108 positioned between proximal section 104 and distal section 106. In the exemplary embodiment, valve 108 includes a first end portion 110 and a second end portion 1 12. Valve 108, in the exemplary embodiment, is configured to control the flow of a fluid, such as CSF, from the ventricle and within catheter 107 to peritoneal cavity 103. For example, valve 108 may be a fixed pressure valve or, alternatively, valve 108 may be modulated in an open, partially open, closed, and/or partially closed position such that the flow of the fluid may vary within catheter 107. Alternatively, valve 108 may be modulated in any other manner that enables shunt system 101 to function as described herein. In addition, valve 108 may be operated manually by a user and/or or valve 108 may be operated via a control system (not shown), such as a computing device, that may be communicatively coupled to valve 108. [0027] In the exemplary embodiment, shunt system 101 also includes a distal catheter 114 that is positioned in distal section 106 and is coupled, in flow communication, with second end portion 112 of valve 108. More specifically, in the exemplary embodiment, distal catheter 114 is positioned within the peritoneal cavity 103 of patient 102. In the exemplary embodiment, distal catheter 1 14 is configured to channel fluid, such as CSF, within tubing 1 15 that extends from catheter 107 to peritoneal cavity 103. Alternatively, distal catheter 114 may be positioned in any other portion of patient 102, such as in the right atrium (not shown) of the heart (not shown), that enables shunt system 101 to function as described herein. Shunt system 101 may also be positioned outside patient 102.

[0028] Monitoring system 100, in the exemplary embodiment, includes a flow monitoring apparatus 120 that is coupled between catheter 107 and valve 108. More specifically, flow monitoring apparatus 120 may be coupled to first end portion 1 10 of valve 108 and catheter 107. Monitoring system 100 also includes a computing device 122 selectively coupled to flow monitoring apparatus 120. In the exemplary embodiment, computing device 122 may be any type of computing device, such as a netbook, a desktop computing device, a laptop computer, or a handheld computing device. As such, computing device 122 includes a user interface 124 that is configured to receive at least one input from a user. In the exemplary embodiment, user interface 124 may include a keyboard, a pointing device, a mouse, a stylus, a touch sensitive panel (e.g., a touch pad or a touch screen), a gyroscope, an accelerometer, a position detector, and/or an audio input interface (e.g., including a microphone). Computing device 122 also includes a processor 126, a communication interface 127, a memory device 128, and a presentation interface 130.

[0029] In the exemplary embodiment, processor 126 is coupled to user interface 124, communication interface 127, memory device 128, and presentation interface 130 via a system bus 136. In the exemplary embodiment, processor 126 communicates with a user, such as by prompting the user via presentation interface 130 and/or by receiving user inputs via user interface 124. In the exemplary embodiment, presentation interface 130 includes a display adapter 140 that is coupled to at least one display device 142. More specifically, in the exemplary embodiment, display device 142 may be a visual display device known in the art.

[0030] Moreover, in the exemplary embodiment, processor 126 is programmed by encoding an operation using one or more executable instructions and providing the executable instructions in memory device 128. Processor 126 can also communicate with flow monitoring apparatus 120 via communication interface 127.

[0031] The term "processor" refers generally to any programmable system including systems and microcontrollers, reduced instruction set circuits (RISC), application specific integrated circuits (ASIC), programmable logic circuits (PLC), and any other circuit or processor capable of executing the functions described herein. The above examples are exemplary only, and thus are not intended to limit in any way the definition and/or meaning of the term "processor."

[0032] In the exemplary embodiment, memory device 128 includes one or more devices that enable information, such as, but not limited to executable instructions and/or other data, to be stored and retrieved. Moreover, in the exemplary embodiment, memory device 128 includes one or more computer readable media, such as, without limitation, dynamic random access memory (DRAM), static random access memory (SRAM), a solid state disk, and/or a hard disk. In the exemplary embodiment, memory device 128 stores, without limitation, application source code, application object code, configuration data, additional input events, application states, assertion statements, validation results, and/or any other type of data. More specifically, in the exemplary embodiment, memory device 128 stores input data received by a user via user interface 124, and/or information/data received from flow monitoring apparatus 120.

[0033] In the exemplary embodiment, various connections may be available between flow monitoring apparatus 120 and computing device 122, including but not limited to a low- level serial data connection, such as Recommended Standard (RS) 232 or RS-485, a high-level serial data connection, such as Universal Serial Bus (USB) or Institute of Electrical and Electronics Engineers (IEEE®) 1394, a parallel data connection, such as IEEE® 1284 or IEEE® 488, a short-range wireless communication channel such as BLUETOOTH®, and/or a private (e.g., inaccessible system) network connection, whether wired or wireless.

[0034] During operation, shunt system 101 enables the removal of excess fluid from the brain. More specifically, by being positioned within the ventricle in the brain, catheter 107 is able to channel fluid, such as CSF, from within the ventricle through flow monitoring apparatus 120 and through valve 108 to distal catheter 1 14 via tubing 115. The fluid is able to exit through distal catheter 1 14 to peritoneal cavity 103, wherein the fluid may be reabsorbed by patient 102. [0035] As explained in more detail below with respect to FIGS. 2-4, in order to ensure shunt system 101 is working properly and there are no blockages within shunt system 101, monitoring system 100 monitors shunt system 101 by measuring the flow rate of CSF within shunt system 101. More specifically, flow monitoring apparatus 120 uses a light source for performing spectroscopic measurements, such as Raman spectroscopy, to determine the flow rate within shunt system 101. Flow monitoring apparatus 120 transmits the data for the detected measurements to computing device 122. Upon receiving the data, computing device 122 generates an output of the spectroscopic measurements for display to a user to enable the user to determine a flow rate of the fluid within shunt system 101. If the flow rate is less than or greater than the standard or normal flow rate, the user can intervene and perform the necessary tasks to repair shunt system 101. For example, the user may adjust valve 108 and/or remove any blockages to adjust the flow rate.

[0036] Because flow monitoring apparatus 120 is coupled directly to shunt system 101, monitoring system 100 enables a non-invasive approach to directly measure the flow rate within shunt system 101. Moreover, healthcare professionals can readily identify any problems within shunt system 101 using this approach and intervene quickly to make any necessary repairs. Accordingly, monitoring system 100 enables a non- invasive and relatively quick approach to measuring the flow rate within shunt system 101 to determine whether shunt system 101 is working appropriately.

[0037] FIG. 2 is an exploded perspective view of flow monitoring apparatus 120. FIG. 3 is a cross-sectional view of a portion of flow monitoring apparatus 120 taken along line 3-3 (shown in FIG. 2). As shown in FIG. 2, in the exemplary embodiment, flow monitoring apparatus 120 includes a conduit assembly 200 that is configured to couple directly with shunt system 101 (shown in FIG. 1). For example, in the exemplary embodiment, conduit assembly 200 is coupled to shunt system 101 such that conduit assembly 200 becomes an intervening component in tubing 115 (shown in FIG. 1). In the exemplary embodiment, conduit assembly 200 includes at least one conduit, such as conduits 201, 202, and 203. While three conduits 201, 202, and 203 are illustrated in the exemplary embodiment, conduit assembly 200 may include any suitable number of conduits that enables flow monitoring apparatus 120 and/or monitoring system 100 (shown in FIG. 1) to function as described herein. For example, flow monitoring apparatus 120 may include six conduits or flow monitoring apparatus 120 may include only one conduit. [0038] Conduit 201 defines a channel (also referred to herein as an opening) 204 that extends therethrough to allow a fluid flow. Similarly, conduit 202 defines an opening 205 that extends therethrough and conduit 203 defines an opening 206 that extends therethrough. Each channel 204, 205, and 206 has a diameter that enables flow monitoring apparatus 120 and/or monitoring system 100 to function as described herein. Each diameter may be equal to each other or each diameter may vary. In one suitable embodiment, each channel 204, 205, and 206 has a diameter of 0.8 millimeters (mm). Moreover, in the exemplary embodiment, conduits 201, 202, and 203 are connected in series such that channels 204, 205, and 206 are concentrically aligned with respect to each other. As such, when conduit assembly 200 is coupled to shunt system 101, fluid within shunt system 101 can flow through the channels 204, 205, and 206.

[0039] Conduits 201, 202, and 203, in the exemplary embodiment, may be composed of any material that may integrate with shunt system 101 and be compatible with the fluid, such as CSF, being channeled therethrough, and suitable for implantation into patient 102 (shown in FIG. 1). For example, conduits 201, 202, and 203 may be composed of polymers, such as, but not limited to silicone, polyurethane (PU), polyethylene (PE), polyvinylchloride (PVC), polytetrafluoroethylene (PTFE), and polyamides, such as nylon.

[0040] In the exemplary embodiment, a substantially cylindrical connecting device 210 is coupled to conduit assembly 200 to facilitate connecting conduit assembly 200 to shunt system 101. More specifically, connecting device 210 is coupled to conduit 201 to facilitate coupling conduit 201 to catheter 107 (shown in FIG. 1) of shunt system 100. Connecting device 210 may be composed of any material that may integrate with shunt system 101 and be compatible with the fluid being channeled therethrough. For example, connective device 210 may be composed of the same materials as conduit assembly 200.

[0041] A silicone tubing portion 212 that is substantially cylindrical is coupled to conduit assembly 200 to facilitate connecting conduit assembly 200 to shunt system 101. More specifically, in the exemplary embodiment, silicone tubing portion 212 is coupled to conduit 203 to facilitate coupled conduit 203 to first end portion 1 10 (shown in FIG. 1) of valve 108 (shown in FIG. 1). Moreover, flow monitoring apparatus 120 may include a housing 218 that is configured to enclose at least a portion of conduit assembly 200, connecting device 210, and/or silicone tubing portion 212 therein. For example, in the exemplary embodiment, housing 218 includes a cavity (not shown) defined therein such that conduits 201, 202, and 203 are substantially enclosed within the cavity of housing 218. Housing 218 may be composed of any material that may integrate with shunt system 101 and be compatible with the fluid being channeled therethrough. For example, housing 218 may be composed of the same materials as conduit assembly 200.

[0042] Each conduit 201, 202, and 203, includes a material exhibiting a strain-sensitive Raman scattering signal. As used herein, a "material exhibiting a strain-sensitive Raman scattering signal" refers to materials that exhibit a shift in the position (i.e., frequency) and/or intensity of Raman bands upon deformation. As used herein, "strain-sensitive" refers to changes of chemical bonds of the material such as, for example, bending and stretching that changes the wave number. Materials that exhibit strain-sensitive Raman bands can be, for example, nanocarbons (such as, for example, carbon nanotubes and graphene), silicon (such as, for example, silicon nanowires and thin films) semiconducting nanowires (such as for example, zinc oxide (ZnO) and gallium nitride (GaN)) in the form of flaps, tubes, wires, thin films and capsules.

[0043] Each material exhibiting a strain-sensitive Raman scattering signal can be, for example, a flap 300 (shown in FIG. 3) that is positioned within channels 204, 205, and 206, respectively, such that a total of three materials (such as flaps 300) are included within flow monitoring apparatus 120 and each of the three flaps 300 are positioned in a different conduit 201, 202, and 203. As illustrated in FIG. 3 (only conduit 201 being shown), each flap 300 has a first end portion 302, a second end portion 303, and a middle portion 304 therebetween. The material (such as flap 300) is positioned within respective channels 204, 205, and 206, such that first end portion 302 is in contact with a portion of respective conduit 201, 202, and 203 and middle portion 304 and second end portion 303 each extend outwardly from first end portion 302 such that middle portion 304 and second end portion 303 are in contact with the fluid when the fluid flows through channels 204, 205, and 206, as shown by arrow 305.

[0044] Moreover, at least a portion of middle portion 304 and second end portion 303 of flap 300 is configured to deform when the fluid is in contact with the material (such as flap 300). More specifically, the material (such as flap 300) is deformed by the drag forces of the fluid flow. In order for the material (such as flap 300) to strain detectably under the drag forces, the material (such as flap 300) is constructed as, in one suitable embodiment, a polyelectrolyte nano-membrane. More specifically, in the exemplary embodiment, each flap 300 includes an exterior surface 308 that includes a plurality of carbon nanotubes, for example, that are embedded therein. In addition to carbon nanotubes, the material exhibiting a strain- sensitive Raman scattering signal can be, for example, can be prepared using other materials such as, for example, graphene, silicon, ZnO and GaN in the form of flaps, tubes, wires, thin films and capsules. Each strain-sensitive material (such as flap 300) may have any suitable dimension that enables flow monitoring apparatus 120 and/or monitoring system 100 to function as described herein. For example, each material (such as flap 300) may have a width of approximately 190 micrometers (μιη). Each material (such as flap 300) may have a height of 600 μιη, wherein 300 μιη defines first end portion 302 that is used for mounting onto conduits 201, 202, and 203, and 300 μιη defines middle portion 304 and second end portion 303 that each are used for contact with the fluid flow. Each material (such as flap 300) may have a thickness of 65 nanometers (nm).

[0045] Moreover, in the exemplary embodiment, each flap 300 (i.e., the polyelectrolyte nano-membrane) is formed by building up alternating layers of oppositely charged polyelectrolytes, such as poly(allylamine hydrochloride) (PAH), and poly(sodium 4- styrenesulfonate) (PSS) on a silicone wafer (not shown), wherein the silicone wafer may be 3 inches. Such polyelectrolytes are polymers with electrolyte repeating units. As such, when dissolved in solution, the polymers become charged. Due to their charged nature, the alternating layers of polyelectrolytes bind tightly to one another to create a relatively strong and relatively thin membrane.

[0046] The membrane may be formed by spin coating a layer of cellulose acetate in a 1% acetone solution onto the surface of the wafer. As such, a charge surface is created for the subsequent layers of polyelectrolyte to bind to. The layer of cellulose acetate is soluble in acetone to facilitate removal of the membrane from the wafer upon completion. Layers of polyelectrolyte are then spin coated onto the wafer. In some embodiments, a solution that includes 0.2 wt% polyelectrolyte in 18ΜΩ distilled water is deposited onto the surface of wafer and then spin coated. Every polyelectrolyte solution may then be spin coated at, for example, 3000 rpm for 15 seconds. A drying step may also be included in which the solution is spun at 2000 rpm for 30 seconds.

[0047] In one embodiment, carbon nanotubes functionalized with carboxylate groups may be used to facilitate binding to the polyelectrolyte layers. The carbon nanotubes may be prepared using techniques known in the art, such as the chemical vapor deposition technique. The membrane can be formed using the general formula (PAH/PSS)i₅PAH/CNT/(PAH/PSS)₅PAH. The nanotubes are offset from the center of the membrane so they strain or deform in tension when placed in the fluid flow and, therefore, enabling substantially accurate detection of relatively low flow rates.

[0048] In exemplary another embodiment, the material can be an array of at least one polyelectrolyte nanotube. The polyelectrolyte nanotube can be prepared using a layer-by-layer assembly of polyelectrolyte materials. For example, a porous membrane can be used as a template to prepare polyelectrolyte nanotubes vertically oriented on the porous membrane to form a nanotube array. The layer-by-layer assembly includes immersion of the membrane in a first polyelectrolyte solution followed by immersion of the membrane in a second polyelectrolyte solution. The first polyelectrolyte solution and the second polyelectrolyte solution are oppositely charged polyelectrolyte solutions. Alternate immersion in the first polyelectrolyte solution followed by immersion of the membrane in the second polyelectrolyte solution results in alternate absorption of the polyelectrolyte causing a build-up of polymer nanotubes. Suitable polyelectrolyte solutions can be, for example, a cationic polyelectrolyte solution and an anionic polyelectrolyte solution. Particularly suitable cationic polyelectrolyte solutions and anionic polyelectrolyte solutions can be, for example, poly(allylamine hydrochloride) poly(diallyldimethylammonium chloride), chitosan, poly(2-vinyl pyridine), poly(acrylic acid) and poly(styrene sulfonate).

[0049] In another exemplary embodiment, graphene oxide can be incorporated into the polyelectrolyte nanotube. Graphene oxide layers can be synthesized by oxidative exfoliation of graphite flakes as described in Kulkarni et al. (ACS Nano 2010, 4, 4667) and Park (Nat. Nano 2009, 4, 217), which are incorporated herein by reference to the extent that they are consistent with the disclosure herein. The concentration and size of graphene oxide layers can suitably be controlled by successive cycles of centrifugation and sonication.

[0050] In a particularly suitable embodiment, graphene oxide layers can be modified to enhance the Raman signals emitted by the graphene oxide. A particularly suitable modification can be, for example, the formation of metal nanostructures on the graphene oxide layer. Metal nanostructures used for Raman spectroscopy are known to those skilled in the art. For example, metal nanostructures can be, for example, metal nanoparticles, metal nanostars, metal nanospheres, metal nanocylinders, metal nanowires, metal nanopyramids, metal nanobipyramids, metal nanorods and combinations thereof. Metals for preparing metal nanostructures used for Raman spectroscopy are known to those skilled in the art. For example, metals that are suitable for preparing metal nanostructures can be, for example, gold, silver and copper.

[0051 ] A particular exemplary embodiment includes the formation of graphene oxide- gold nanostar. To prepare graphene oxide-gold nanostar nanopatches, a gold precursor such as, for example, HAuCl₄, can be reduced in the presence of graphene oxide using (4-(2- hydroxyethyl)-l-piperazineethanesulfonic acid (HEPES). Without being bound by theory, it is believed that graphene oxide serves as a flexible soft template for surface-mediated growth of the gold nanostars. HEPES allows for the reduction of HAuC , in aqueous phase through the oxidation of its N-substituted piperazine ring to an N-centered cationic free radical, producing gold nanostructures. The gold nanostars form patches on the graphene oxide surface. Changing the graphene oxide to gold ratio allows for the density of gold nanostructures and the localized surface plasmon resonance (LSPR) of the gold nanostructures on the graphene oxide layers to be tuned from visible to near infrared wavelength range. For example, increasing the graphene oxide to gold ratio can be used to enhance nucleation (increase the density of gold nanostructures on graphene oxide) and increase the anisotropy (spike size) of the gold nanostructures, both of which can result in a red-shift in the LSPR wavelength. The Raman bands from graphene oxide layers modified with a metal nanostructure can be enhanced up to about 300% as compared to unmodified graphene oxide layers (without metal nanostructures).

[0052] In a particularly suitable material exhibiting a strain-sensitive Raman signal, graphene oxide-metal nanostructures can be incorporated into at least one layer of the polyelectrolyte layers. For example, polyelectrolyte layers can be formed on a template material as described herein. Vacuum infiltration can then be used to infiltrate the graphene oxide-metal nanostructures into the polyelectrolyte layer(s) following the deposition of polyelectrolyte as described herein. After infiltration of the graphene oxide-metal nanostructures another polyelectrolyte layer can be deposited over the graphene oxide-metal nanostructures if desired. In this manner, graphene oxide-metal nanostructures can be sandwiched between polyelectrolyte layers. Following deposition of polyelectrolyte layers and incorporation of graphene oxide-metal nanostructures, the template upon which the polyelectrolyte layers either with or without graphene oxide-metal nanostructures are formed is dissolved to free the material.

[0053] In some embodiments, photolithography and reactive ion etching may be used to accurately shape the membrane. For example, a photoresist may be spin coated onto the top layer of the wafer. It is exposed to ultraviolet (UV) light in the pattern of the desired size and shape of the membrane. The UV light facilitates the formation of a protective layer of photoresist over the desired membrane. The membrane is then cut to shape using reactive ion etching, where oxygen plasma is used to remove unwanted pieces of membrane for the construction of each flap 300. Once flaps 300 are constructed, each flap 300 can be mounted within a separate conduit 201, 202, and 203. For example, each flap 300 can be adhered onto a portion of each conduit 201, 202, and 203, within openings 204, 205, and 206, respectively, as shown in FIG. 3.

[0054] Referring to FIG. 3, a laser 320 is positioned proximate to the material (such as flap 300). In the exemplary embodiment, laser 320 may be any suitable laser known in the art, such as an ultrafast laser or a monochromatic laser, that is configured to direct a light source, as shown by arrow 321, onto exterior surface 308 of material (such as flap 300) to facilitate spectroscopic measurements, such as Raman spectroscopy, to measure the flow rate of the fluid within shunt system 101. In addition, a detector 324 is positioned proximate to material (such as flap 300). In the exemplary embodiment, detector 324 may include any type of suitable transducer that is configured to detect the scattering of the light source, as shown by arrow 325, after the light source is directed onto material (such as flap 300). Detector 324 may also be configured to process and/or analyze the scattered light source. Detector 324 is coupled to computing device 122 and is configured to transmit at least one signal representative of the detected data to computing device 122 such that the data can be further analyzed and/or processed and an output of the data can be generated and presented to a user.

[0055] During operation, as fluid, such as the CSF fluid, is being channeled through shunt system 101, the fluid is channeled through flow monitoring apparatus 120. More specifically, the fluid is channeled from catheter 107 to flow monitoring apparatus 120. The fluid flows through channels 204, 205, and 206 of conduits 201, 202, and 203, respectively. The fluid flows across each material (such as flap 300) and causes at least a portion of middle portion 304 and second end portion 303 of each material (such as flap 300) to deform, as each material (such as flap 300) becomes strained from the drag forces of the fluid flow.

[0056] While the fluid flows through channels 204, 205, and 206, laser 320 directs the light source onto exterior surface 308 of each material (such as flap 300), as shown by arrow 322. As the light source comes into contact with surface 308, the light is scattered, as shown by arrow 325, and this scattering is detected by detector 324. More specifically, the spectra of light scattered from material (such as flap 300) is detected by detector 324. In one embodiment, the majority of the incident light may be scattered elastically, at the same wavelength as the incident light (i.e., Rayleigh Scattering), and may be filtered out by detector 324. Depending on the how material (such as flap 300) deforms, a small portion of the scattered light undergoes a slight wavelength shift relative to the incident light. Detector 324 detects and/or analyzes the intensities of the light scattered at each wavelength shift. Detector 324 then transmits the detected data to computing device 122.

[0057] When computing device 122 receives the data, computing device 122 may further analyze and/or process the data. More specifically, computing device 122 generates an output 400 (shown in FIG. 4) representative of the detected data and output 400 may be presented to a user via display device 142 (shown in FIG. 1). In the exemplary embodiment, output 400 is a graphical representation of a Raman spectra of the carbon nanotubes that displays a shift in wavelength intensities. By looking at the Raman spectra, a user can identify whether the deformation of the material (such as flap 300) caused by the fluid flow results in a deformation of the material (such as flap 300), and the identification of the strain facilitates a determination of a flow rate of the fluid. For example, output 400 may include a standard peak 402, which represents minimal to no strain on the material (such as flap 300) when fluid flow within shunt system 101 is occurring at a normal rate. Output 400 may also include the test peak 404, which can be compared with standard peak 402. In the exemplary embodiment, test peak 404 is representative of the data described above that was obtained from flow monitoring apparatus 120. Test peak 404 has a different wavelength from standard peak 402, as test peak 404 is shifted to the left from standard peak 402. As such, test peak 404 indicates that each flap 300 is bent such that each flap 300 is strained and that the fluid is flowing within shunt system 101 at a faster rate than the normal or standard flow rate. As such, the user may need to immediately intervene and perform a revision or repair of shunt system 101 to correct the flow rate.

[0058] In another aspect, the present disclosure is directed to a method for monitoring fluid flow within a flow conduit system. The method comprises coupling at least one conduit to a flow conduit system, the at least one conduit defining a channel for fluid flow within the flow conduit system, wherein a material exhibiting a strain-sensitive Raman scattering signal is positioned within the channel and wherein at least a portion of the material is configured to deform when the fluid flows through the channel; directing light from a light source onto the material to generate a spectroscopic signal to detect deformation of the strain-sensitive material; generating an output of the spectroscopic signal, via a computing device; and displaying the output of the spectroscopic signal, via the computing device, to a user. The method for monitoring fluid flow within a flow conduit system can be used, for example, to identify whether the material is deformed. The method for monitoring fluid flow within a flow conduit system can also be used, for example, to identify how much the material is deformed.

[0059] In an exemplary embodiment, the flow conduit system can be a shunt system. The shunt system can be, for example, a ventriculoperitoneal shunt system. In other exemplary embodiments, the flow conduit system can be, for example, a vascular graft, an arteriovenous fistula, a vascular stent, and an artificial valve.

[0060] As compared to known monitoring techniques for monitoring shunt systems, the above-described monitoring system is enabled to provide a non-invasive and relatively quick approach to measuring the rate of the fluid flow within a flow conduit system such as, for example, shunt systems. More specifically, the monitoring system includes a flow monitoring apparatus and a computing device that is coupled to the flow monitoring apparatus. The flow monitoring apparatus is coupled directly to the shunt system and uses a light source for performing spectroscopic measurements to determine the flow rate within the shunt system. The computing device is configured to generate an output of the spectroscopic measurements for display to a user to enable the user to determine the flow rate of the fluid within the flow conduit system. Based on the flow rate, the user can then identify whether the flow conduit system is working appropriately. Because the flow monitoring apparatus is coupled directly to the flow conduit system, using such a monitoring system enables a non-invasive approach to directly measure the flow rate within the flow conduit system. Moreover, healthcare professionals can readily identify any problems with the flow conduit system without having to perform any procedures, such as surgical procedures.

[0061] Exemplary embodiments of the systems, apparatus, and methods are described above in detail. The systems, apparatus, and methods are not limited to the specific embodiments described herein, but rather, components of the systems and/or apparatus and/or steps of the method may be utilized independently and separately from other components and/or steps described herein. For example, the system may also be used in combination with other systems and methods, and is not limited to practice with only a monitoring system as described herein. Rather, the exemplary embodiment can be implemented and utilized in connection with many other systems. EXAMPLES

EXAMPLE 1

[0062] In this Example, polymer nanotubes were prepared to form a strain-sensitive material.

[0063] In particular, porous alumina membranes were employed as templates to obtained vertical array of polyelectrolyte multilayer nanotubes. Poly (ally lamine hydrochloride) (PAH) and poly(styrene sulfonate) (PSS) as cationic and anionic polyelectrolyte solutions were used for layer-by-layer assembly. Commercially acquired polyelectrolyte (power) was dissolved in water at a concentration of 0.2% w/v to prepare the polyelectrolyte solutions. Polyelectrolytes were infiltrated into the porous alumina membranes and adsorbed onto the walls by alternately immersing the membranes into the cationic and anionic polyelectrolyte solutions for 10 min at room temperature followed by extensive rinsing with water. Alternate adsorption of the oppositely charged (cationic and anionic) polyelectrolytes resulted in the build-up of polymer nanotubes. FIG. 5 shows the vertical array of nanotubes formed through the layer-by-layer assembly of polyelectrolytes (the nanotubes are partially collapsed due to capillary forces that occured during drying process).

EXAMPLE 2

[0064] In this Example, graphene oxide layers are modified to include gold nanostars to enhance the Raman signals from the graphene oxide.

[0065] In particular, gold precursor (HAuCU) was reduced in the presence of graphene oxide using (4-(2-hydroxyethyl)-l-piperazineethanesulfonic acid (HEPES) as illustrated in FIG. 6. The gold nanostars form patches on the graphene oxide surface (FIGS. 7A and 7B). FIG. 7C shows a high resolution SEM image of the gold nanostars. Atomic force microscopy was also used to obtain an image of the graphene oxide-gold nanostars (FIG. 7D). Changing the graphene oxide to gold ratio allowed for the density of gold nanostructures and the LSPR of the gold nanostructures on the graphene oxide layers to be tuned from visible to near infrared (MR) wavelength range (FIG. 8A). Tuning the LSPR of photothermal contrast agents to NIR therapeutic window (650-900 nm), where the endogenous absorption coefficient of tissue is nearly two orders of magnitude lower compared to the visible part of EM spectrum, is significant for photothermal therapy of deep tissues. As shown in FIG. 8B, the Raman bands from graphene oxide-gold nanostar layers ("GO-AuNS") exhibited nearly 300% enhancement as following the formation of the gold nanoparticles as compared to graphene oxide without gold nanoparticles ("GO") and gold nanostars ("AuNS").

[0066] Although specific features of various embodiments of the invention may be shown in some drawings and not in others, this is for convenience only. In accordance with the principles of the invention, any feature of a drawing may be referenced and/or claimed in combination with any feature of any other drawing.

[0067] This written description uses examples to disclose the invention, including the best mode, and also to enable any person skilled in the art to practice the invention, including making and using any devices or systems and performing any incorporated methods. The patentable scope of the invention is defined by the claims, and may include other examples that occur to those skilled in the art. Such other examples are intended to be within the scope of the claims if they have structural elements that do not differ from the literal language of the claims, or if they include equivalent structural elements with insubstantial differences from the literal language of the claims.

Claims

WHAT IS CLAIMED IS:

1. A flow monitoring apparatus for monitoring fluid flow within a flow conduit system, the flow monitoring apparatus comprising:

at least one conduit configured to couple to the flow conduit system, the at least one conduit defining a channel for a fluid flow;

a material exhibiting a strain-sensitive Raman scattering signal positioned within the channel, wherein at least a portion of the material is configured to deform when the fluid flows through the channel; and

a light source configured to direct light onto the material to generate a spectroscopic signal to detect deformation of the material.

2. The flow monitoring apparatus of claim 1, further comprising a detector to measure the spectroscopic signal.

3. The flow monitoring apparatus of claim 1, wherein the material comprises a plurality of carbon nanotubes.

4. The flow monitoring apparatus of claim 1, wherein the spectroscopic signal comprises a Raman spectra.

5. The flow monitoring apparatus of claim 1, wherein the material comprises a polyelectrolyte nanotube.

6. The flow monitoring apparatus of claim 5, wherein the polyelectrolyte nanotube comprises at least one graphene oxide layer.

7. The flow monitoring apparatus of claim 6, wherein the at least one graphene oxide layer comprises a metal nanostructure.

8. The flow monitoring apparatus of claim 7, wherein the metal nanostructure is selected from the group consisting of a gold nanostructure, a silver nanostructure and a copper nanostructure.

9. The flow monitoring apparatus of claim 7, wherein the metal nanostructure is selected from the group consisting of a metal nanostar, a metal nanoparticle, a metal nanosphere, a metal nanocylinder, a metal nanowire, a metal nanopyramid, a metal nanobipyramid, a metal nanorod and combinations thereof.

10. A monitoring system for monitoring fluid flow within a flow conduit system, the monitoring system comprising:

a flow monitoring apparatus comprising:

a material exhibiting a strain-sensitive Raman scattering signal positioned within the channel, wherein at least a portion of the material is configured to deform when the fluid flows through the channel;

a light source configured to direct light onto the material to generate a spectroscopic signal to detect deformation of the strain-sensitive material; and

a computing device coupled to the flow monitoring apparatus configured to generate an output of the spectroscopic signal for display to a user.

1 1. The flow monitoring apparatus of claim 10, wherein the material comprises a polyelectrolyte nanotube.

12. The flow monitoring apparatus of claim 1 1, wherein the polyelectrolyte nanotube comprises at least one graphene oxide layer.

13. The flow monitoring apparatus of claim 12, wherein the at least one graphene oxide layer comprises a metal nanostructure.

14. The flow monitoring apparatus of claim 13, wherein the metal nanostructure is selected from the group consisting of a gold nanostructure, a silver nanostructure and a copper nanostructure.

15. The flow monitoring apparatus of claim 13, wherein the metal nanostructure is selected from the group consisting of a metal nanostar, a metal nanoparticle, a metal nanosphere, a metal nanocylinder, a metal nanowire, a metal nanopyramid, a metal nanobipyramid, a metal nanorod and combinations thereof

16. The flow monitoring apparatus of claim 10, further comprising a detector to measure the spectroscopic signal.

17. The flow monitoring apparatus of claim 10, wherein the computing device is configured to generate a Raman spectra.

18. A method for monitoring fluid flow within a flow conduit system, the method comprising:

coupling at least one conduit to the flow conduit system, the at least one conduit defining a channel for fluid flow within the flow conduit system, wherein a material exhibiting a strain-sensitive Raman scattering signal is positioned within the channel and wherein at least a portion of the material deforms when the fluid flows through the channel;

directing light from a light source onto the material to generate a spectroscopic signal to detect deformation of the material;

generating an output of the spectroscopic signal, via a computing device; and displaying the output of the spectroscopic signal, via the computing device, to a user.

19. The method of claim 18, further comprising measuring the scattering of light when the light source is directed onto the material.

20. The method of claim 18, wherein generating an output of the spectroscopic signal further comprises generating a Raman spectra.