Abstract:
A gamma ray detector includes a gamma ray detecting rod elongated along a longitudinal axis, wherein gamma ray detection is enhanced along the longitudinal axis, and a gamma ray shield encapsulating the rod, the shield having an aperture at an end of the detecting rod along the longitudinal axis to admit gamma rays substantially parallel to the longitudinal axis of the elongated detecting rod, wherein gamma ray detection is enhanced along the longitudinal axis and aperture to substantially collimate the sensitivity of the gamma ray detector along the combined aperture and longitudinal axis of the detecting rod.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     This application claims priority to U.S. Provisional Patent Application No. 61/508,402 entitled “RADIOPHARMACEUTICAL CZT SENSOR AND APPARATUS” filed on Jul. 15, 2011; and U.S. Provisional Patent Application No. 61/508,294 entitled “SYSTEMS, METHODS, AND DEVICES FOR PRODUCING, MANUFACTURING, AND CONTROL OF RADIOPHARMACEUTICALS-FULL” filed on Jul. 15, 2011. The entirety of each of the preceding applications is incorporated by reference herein. 
    
    
     BACKGROUND 
     I. Field 
     Aspects of the present invention relate generally to gamma ray sensors, and more particularly to methods and devices for detecting radioisotope concentration, activity and volume using gamma ray detection with cadmium zinc telluride (CZT) solid state detectors. 
     II. Background 
     Diagnostic techniques in nuclear medicine generally use radioactive tracers which emit gamma rays from within the body. These tracers are generally short-lived isotopes linked to chemical compounds which permit specific physiological processes to be studied. These compounds, which incorporate radionuclides, are known as radiopharmaceuticals, and can be given by injection, inhalation or orally. One type of diagnostic technique includes detecting single photons by a gamma-ray sensitive camera which can view organs from many different angles. The camera builds an image from the points from which radiation is emitted, and the image is electronically enhanced and viewed by a physician on a monitor for indications of abnormal conditions. 
     A more recent development is Positron Emission Tomography (PET), which is a more precise and sophisticated technique using isotopes produced in a cyclotron, where protons are introduced into the nucleus resulting in a deficiency of neutrons (i.e., becoming proton rich). 
     The nucleus of a radioisotope usually becomes stable by emitting an alpha and/or beta particle (or a positron). These particles may be accompanied by the emission of energy in the form of electromagnetic radiation known as gamma rays. This process is known as radioactive decay. 
     A positron-emitting radionuclide is introduced into the body of a patient, usually by injection, and accumulates in the target tissue. As the radionuclide decays, a positron is emitted, and the emitted positron combines with a nearby electron in the target tissue, resulting in the simultaneous emission of two identifiable gamma rays in opposite directions, each having an energy of 511 keV. These gamma rays are conventionally detected by a PET camera, and provide a very precise indication of their origin. PET&#39;s most important clinical role is typically in oncology, with fluorine-18 (F-18) as the tracer, since F-18 has proven to be the most accurate non-invasive method of detecting and evaluating most cancers. Fluorine-18 (F-18) is one of several positron emitters (including also, Carbon-11, Nitrogen-13, and Oxygen-15) that are produced in a cyclotron and are used in PET for studying brain physiology and pathology, in particular for localizing epileptic focus, and in dementia, psychiatry and neuropharmacology studies. These positron emitters also have a significant role in cardiology. F-18 in FDG (fluorodeoxyglucose) has become very important in detection of cancers and the monitoring of progress in cancer treatment, using PET. A radioactive product such as F-18 in FDG is a specific example of a radiopharmaceutical. 
     F-18 has a half-life of approximately 110 minutes, which is beneficial in that it does not pose a long-term environmental and/or health hazard. For example, after 24 hours, the radioactivity level is approximately 0.01% of the product when freshly produced in a cyclotron. However, transport time from the production source to clinical use should be minimized to retain a maximum potency for accurate diagnostic value. 
     Whereas PET cameras are effective in imaging uptake of F-18 present in administered FDG, PET cameras are generally too large and ineffective in production settings where characterization of the source product, and not physiological response, is the goal. There is a need, therefore, for a method and apparatus to timely calibrate the radioactivity of a sample at the production source and time of production or packaging for delivery so that the level of radioactivity is predictably known at the time of use. 
     SUMMARY 
     The following presents a simplified summary of one or more aspects of a method and apparatus for detecting radioisotope concentration, activity and sample volume. 
     In one example aspect of the invention, a gamma ray detector may include a gamma ray detecting rod elongated in one direction to a specified length, and a gamma ray shield encapsulating the rod, the shield having an opening opposite an end of the elongated rod to admit gamma rays substantially parallel to the long axis of the elongated rod, wherein the long axis of the rod and the opening are directed toward a volume of gamma ray emitting material observable by the detector on the basis of the length of the elongated rod and the opening in the gamma ray shield. 
     In another example aspect of the disclosure, an apparatus for detecting a volume concentration and activity of a radionuclide content in a container includes a container of known dimensions for receiving the radionuclide. A first gamma ray detector is arranged below the container with respect to gravity and directed toward the container. A second gamma ray detector is arranged above the container with respect to gravity and opposite the first gamma ray detector, and directed toward the container. Detection circuitry and a processor are coupled to the first and second gamma ray detectors, wherein the processor is configured to measure radiation intensity received at the first and second gamma ray detectors and determine a level of content of radionuclide in the container on the basis of the radiation detected by the first and second gamma ray detectors. 
     To the accomplishment of the foregoing and related ends, the one or more example aspects comprise the features hereinafter fully described and particularly pointed out in the claims. The following description and the annexed drawings set forth in detail certain illustrative aspects of the one or more aspects. These aspects are indicative, however, of but a few of the various ways in which the principles of various aspects may be employed and the described aspects are intended to include all such aspects and their equivalents. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       These and other sample aspects of the invention will be described in the detailed description that follow, and in the accompanying drawings, wherein: 
         FIG. 1  is a conceptual illustration of a gamma ray collimated detector in accordance with various aspects of the invention; 
         FIG. 2  is a conceptual side illustration of the detector of  FIG. 1 , in accordance with various aspects of the invention; 
         FIG. 3  is a conceptual circuit diagram for measuring gamma rays with the detector of  FIGS. 1 and 2 , in accordance with various aspects of the invention; 
         FIG. 4  is a conceptual illustration of an apparatus for measuring concentration, activity and content volume of a radiopharmaceutical using the detector and circuitry of  FIGS. 1-3  in accordance with various aspects of the invention; 
         FIG. 5  presents a conceptual processing system for measuring the content volume of the radiopharmaceutical in the apparatus of  FIG. 4 , in accordance with various aspects of the invention; 
         FIG. 6  presents a flowchart of the functions of components of a flexible programmable gate array (FPGA) of the processing system of  FIG. 5 , in accordance with various aspects of the invention; 
         FIG. 7  is a plot of gamma ray activity in counts per second (cps) of a top detector and a bottom detector of the apparatus in  FIG. 3  as a container between the two detectors is filled, in accordance with various aspects of the invention; 
         FIG. 8  is a logarithmic plot of the ratio of counts in the top detector to the bottom detector as a function of fill level in the container of the apparatus of  FIG. 3 , in accordance with various aspects of the invention; 
         FIG. 9  presents an exemplary system diagram of various hardware components and other features, for use in networking the apparatus for measuring concentration, activity and content volume, in accordance with various aspects of the invention; and 
         FIG. 10  is a block diagram of various exemplary system components for providing communications with and between various components of the apparatus for measuring concentration, activity and content volume, in accordance with various aspects of the invention. 
     
    
    
     In accordance with common practice, some of the drawings may be simplified for clarity. Thus, the drawings may not depict all of the components of a given apparatus (e.g., device) or method. Finally, like reference numerals may be used to denote like features throughout the specification and figures. 
     DETAILED DESCRIPTION 
     Various aspects of methods and apparatus are described more fully hereinafter with reference to the accompanying drawings. These methods and devices may, however, be embodied in many different forms and should not be construed as limited to any specific structure or function presented throughout this disclosure. Rather, these aspects are provided so that this disclosure will be thorough and complete, and will fully convey the scope of these methods and apparatus to those skilled in the art. Based on the descriptions herein teachings herein one skilled in the art should appreciate that that the scope of the disclosure is intended to cover any aspect of the methods and apparatus disclosed herein, whether implemented independently of or combined with any other aspect of the disclosure. For example, an apparatus may be implemented or a method may be practiced using any number of the aspects set forth herein. In addition, the scope of the disclosure is intended to cover such an apparatus or method which is practiced using other structure, functionality, or structure and functionality in addition to or other than the various aspects of the disclosure set forth herein. It should be understood that any aspect of the disclosure herein may be embodied by one or more elements of a claim. 
     In a radiopharmaceutical production facility, a cyclotron may be used to prepar a bolus of a material containing a radioisotope of interest which is delivered to a synthesis system. The radioisotope may emit one or more kinds of radiation, including electrons, positrons, gamma rays/x-rays, protons, neutrons, alpha particles, and other possible nuclear ejecta. In one example, a radioisotope, when added to other materials to be administered to a subject, may emit a positron, which then annihilates with an electron, for example, in human tissue, to produce gamma rays. 
     Aspects of the current invention describe a gamma ray detector and methods of measuring the activity, concentration, and volume of a liquid radionuclide as it fills or is drained from a container. In the production of radiopharmaceuticals, the radionuclide may be introduced into a molecular vehicle by chemical synthesis to produce the radiopharmaceutical. Various dosage, concentration, activity and volume requirements for differing medical applications may generally result in splitting, dilution and redistribution of the radioisotope for the production of the various radiopharmaceuticals, wherein a sensor monitors the various production processes. 
       FIG. 1  shows a schematic illustration of a gamma ray collimated detector  100 . According to various aspects, the sensor  100  may include a cadmium zinc telluride (CdZnTe, or CZT) element  110 . However, other solid state materials such as, e.g., other solid state materials, currently available or yet to be discovered may be used. CZT is a direct bandgap semiconductor and can operate in a direct-conversion (e.g., photoconductive) mode at room temperature, unlike some other materials (particularly germanium) which may require cooling, in some cases, to liquid nitrogen temperature. Advantages of CZT over germanium or other detectors include a high sensitivity for x-rays and gamma-rays that is due to the high atomic numbers and masses of Cd and Te relative to atomic numbers and masses of other detector materials currently in use, and better energy resolution than scintillator detectors. A gamma ray (photon) traversing a CZT element  110  liberates electron-hole pairs in its path. In operation and according to various aspects, a bias voltage applied across electrodes  115  (not shown in  FIG. 1 ) and  116  on the surface of the element  110  (both shown in a side view in  FIG. 2 ) causes charge to be swept to the electrodes  115 ,  116  on the surface of the CZT (electrons toward an anode, holes toward a cathode). According to various aspects, wires  125  and  126  may connect electrodes  115  and  116 , respectively, to a source of the applied voltage. 
     According to various aspects, the sensor  100  can function accurately as a spectroscopic gamma energy sensor, particularly when the element  110  is CZT. However, geometric aspects may be considered. In conventional use of CZT as a gamma ray detector, the CZT element  110  may be a thin platelet, sometimes arranged in multiples to form arrays for imaging, generally perpendicularly to the source of gamma ray emission. Therefore, gamma rays of differing energies all traverse a detector element of substantially the same thickness. While absorption of the gamma ray may generally be less than 100% efficient, higher energy gamma rays may liberate more electron-hole pairs than lower energy gamma rays, producing a pulse of greater height. The spectrum and intensity of gamma ray energies may thus be spectroscopically determined by counting the number of pulses generated corresponding to different pulse heights. 
     According to various aspects, because higher energy photons may travel a greater distance in the CZT rod  110  before complete absorption, it is advantageous for the CZT rod  110  to be greater in length in a direction longitudinally (i.e., a long axis) intersecting a known source volume of radionuclide being measured. Gamma rays incident on the CZT rod off or transverse to the long axis may not be fully absorbed, and thus, the CZT rod may not be as sensitive a detector of such gamma rays as a result. Thus, according to various aspects, elongating the CZT rod in one direction introduces a degree of collimation and directional sensitivity along the extended direction. 
     According to various aspects, the absorption coefficient for 511 keV gamma ray absorption in CZT is μ=0.0153 cm 2 /gm. The absorption probability as a function of μ, density ρ (=5.78 gm/cm 3 ) and penetration distance h is
 
 P (μ, h )=1− e   −μρh .
 
     Therefore, the ratio of absorption in a 10 mm length of CZT to a 1 mm length is 
                   P   ⁡     (     μ   ,     10   ⁢           ⁢   mm       )         P   ⁡     (     μ   ,     1   ⁢           ⁢   mm       )         ~   9.613     .         
That is, the directional sensitivity for gamma ray detection of CZT at 511 keV along the 10 mm length of the detector is nearly 10 times greater than in the 1 mm thick transverse direction.
 
     Referring to  FIGS. 1 and 2 , according to various aspects, the sensor may be a CZT rod  110  as described above, encased in a shielded case  105  (e.g., tungsten) with an aperture  120  open and directed toward a vial or other container containing a radiopharmaceutical sample to expose to the CZT rod  110  along the long dimension of the rod  110 , while shielding the CZT rod  110  from gamma rays incident laterally to the long dimension of the rod  110 , e.g., from directions other than along the longitudinal dimension. According to various aspects, the combination of shielding, aperture and extended length of the CZT detector in the direction of gamma ray emission from a portion of the radiopharmaceutical sample provides a substantial directional “virtual” collimation of the CZT detector&#39;s sensitivity to gamma rays incident from a volume of the radiopharmaceutical that is defined by the collimation and the size (e.g., diameter) of the radiopharmaceutical container and the collimation of the acceptance aperture  120  of the detector  100 . According to various aspects, on the basis that the volume of the radiopharmaceutical that is “observable,” or detectable, by the sensor  100  is constant from measurement to measurement, the concentration and activity of the radionuclide can be determined, after calibration. 
       FIG. 3  shows a conceptual circuit diagram for measuring gamma rays with the detector  100 . According to various aspects, a charge amplifier  130  coupled to the electrodes  115  and  116  amplifies the charge. According to various aspects, a pulse generator  140  converts the sensed charge to a pulse, where the pulse height is proportional to the energy of the gamma ray. A counting circuit  150  may determine the number of pulses as a function of energy. 
       FIG. 4  is a conceptual illustration of an apparatus  400  for measuring concentration, activity and content volume in a container  415  containing a radionuclide such as F-18 in solution, or a radiopharmaceutical such as F-18 in FDG, using the detector  100  and circuitry of  FIGS. 1-3 . According to various aspects, the container  415  may have known dimensions, and therefore is known to be able to hold a specified maximum volume of the radionuclide in a liquid form. In operation, according to various aspects, a first detector  100 - b  may be located opposite a bottom face  425 - b  of the container  415 . Similarly, according to various aspects, a second detector  100 - t  may be located opposite a top face  425 - t  of the container, and is similarly configured to detect gamma radiation from the container  415 . According to various aspects, the two detectors  100 - b ,  100 - t  may be similar or substantially the same. According to various aspects, the two detectors may be identical. Both of the detectors  100 - t  and  100 - b  is coupled to a differential measurement processing system  450 , shown in greater detail in  FIG. 5 . 
       FIG. 5  is a block diagram describing the differential processing system  450  coupled to the two detectors,  100 - t ,  100 - b , according to various aspects. The processing system  450  may include a high voltage supply  452  to provide the bias voltage that operates each of the detectors  100 - t ,  100 - b . Charge output from the detectors  100 - t  and  100 - b  are separately input (optionally) to signal conditioning circuitry  452  if noise filtering or DC offset correction, or other artifact removal is warranted. Alternatively, the signals from the detectors  100 - t ,  100 - b  may be directly input to a dual channel analog-to-digital converter (ADC)  456  for processing in digital format by a customized chip, such as a flexible programmable gate array (FPGA)  458 . The function of the FPGA  458  will be discussed further below. Output of the FPGA  458  includes at least computed values for the activity sensed by each of the detectors  100 - t ,  100 - b  and the volume of radionuclide in liquid accumulated in the container  415 . The output of the FPGA  458  may be communicated to a computing platform, such as a personal computer (PC)  460 , or other computing controller for purposes of controlling such processes as filling or emptying the container  415  and identifying parameters associated with the pharmaceutical content for documentation (e.g., date, activity, volume content, labeling, etc.). 
     The processing system  450  may be distributed across a network to facilitate, for example, efficient use of computing resources to serve a plurality of detectors  100  and containers  415 . The division of the processing system  450  across the network may be selected at any of several points. For example, one or more access nodes (not shown) and network links (not shown) may be placed between the dual channel analog-to-digital converter (ADC)  456  and the FPGA  458 , in which case the FPGA  458  and the computing platform PC  460  may be remotely located across the network. Alternatively, the access nodes and network links may be located between the FPGA  458  and the PC  460 . It should be understood that other network linking arrangements between the detectors  100  and computing and control resources may be configured. The PC  460  may also be a network configured computing resource, which may also be distributed across one or more networks. For example, the computing resource PC  460  may include a server, memory, and other accessories, also located remotely from each other across the one or more networks to provide the operational control of the plurality of detectors  100  coupled to respective containers  415 . 
       FIG. 6  is a flowchart  600  describing the functions of components of the FPGA  458 . Digitized data from each channel (i.e., top and bottom) of the ADC  456  is input to respective counters for pulse counting (process block  602 ). In conjunction with a clocking signal from a timing source (not shown) the pulse counts per unit of time (e.g., seconds) are converted to respective count rates (process block  604 ). 
     The count rates are then linearized (in process block  606  for each respective detector  100 - t ,  100 - b ). The linearization process may include statistical or calibration-based correction, for example, when the count rate becomes so high that pulses may overlap, an effect referred to as “pile up.” 
     The measured count rate, as counted by the detector and associated electronics, may become lower than the true count rate at high count rates. This is caused by effects in the bias circuitry, crystal, and the electronics. In the bias circuitry and crystal, a high photon flux can cause a shift in the spectral response (as a decreased photopeak to background ratio) which can cause undercounting. Also, the pulse width (governed by the crystal and preamplifier characteristics) along with the pulse counting electronics can have an impact on linearity. At high count rates, pulses can pile up and double or triple pulses may be combined and counted as one instead of two or three separate pulses respectively. This is exacerbated when the pulse width is increased or the counting electronics is too slow to count fast pulse rates (long retrigger times, etc.). 
     To linearize the count rate, a nonlinearity calibration is performed, along with implementing a look-up table or nonlinearity correction equation. To perform calibration, a high activity sample (e.g., having a maximum expected activity) is placed in front of each sensor and allowed to decay. Data is then collected over several half-lives until the count rate is low (i.e., in the linear range where no pulse pile up occurs). Curve fitting is then performed (e.g., polynomial, Lambert-W, etc.) to describe the relationship between true count rate and the measured count rate. Once established, the curve for each sensor (detector and electronics) can be used in a look-up table or equation-based correction to linearize measurements made. 
     Accordingly, a correction may be applied on a calibration basis to correct for an undercounting of pulses due to pulse overlap. If a background count has been detected (such as, for example, before the container is filled), a command may be issued for each detector rate to read the background rate (in process blocks  608 - t ,  608 - b , whether from a look-up table, a previous reading from the detectors prior to filling the container, etc.). The background rates are subtracted (in process blocks  610 - t  and  610 - b ) from the respective linearized count rates. 
     The ratio of the resulting “adjusted” counting rates is computed (in process block  612 ) and the logarithm of the ratio is computed (in process block  613 ) which, as it happens is approximately linear in proportion to the fill level of the container  415 . In one embodiment, the log ratio measurement may be referred to a lookup table to compute the fill volume of the container (as in process block  614 ). The fill volume depends on a known value of the shape, cross-section and height of the container  415 . The adjusted count rate for each detector is compared with the computed volume to determine the lookup activity (in process blocks  616 - t  and  616 - b ) for each respective detector  100 - t ,  100 - b . The outputs to the PC  460  include the top activity level, bottom activity level, and container volume. 
       FIG. 7  is a plot of gamma ray activity in counts per second (cps) of the top detector  425 - t  and the bottom detector  425 - b  of the apparatus in  FIG. 3  as a container between the two detectors is filled, according to various aspects. Because the two detectors  425 - t  and  425 - b  may be placed opposite each other, they both interrogate substantially a same volume element. When the container  430  is nearly empty, both detectors register substantially zero counts, apart from background counts, however the ratio asymptotically approaches zero, and the logarithmic ratio becomes large negative. When the container  430  is full, both detectors  425 - t ,  425 - b  interrogate substantially the same volume, and therefore register equal counts. Therefore, the ratio between the counts of both detectors  425 - t  and  425 - b  is equal to one, and the logarithmic value of the ratio is thus 0. According to various aspects,  FIG. 8  is a logarithmic plot of the ratio of counts of the top detector  425 - t  to the counts of the bottom detector  425 - b  as a function of fill level in the container  430  of the apparatus  400 . For intermediate levels of fill, the log ratio is approximately linear, and the linearized logarithmic measure of the count ratio may be used to determine the fill volume of the entire container, because it may be assumed that the dimensions and shape of the container  430  is defined (e.g., a cylinder of known constant cross-section area and height). With the fill volume and activity thus determined, the concentration of the radionuclide can be determined. 
     According to various aspects,  FIG. 9  presents an exemplary system diagram of various hardware components and other features, for use in networking the apparatus for measuring concentration, activity and content volume, in accordance with an aspect of the present invention. Computer system  900  may include a communications interface  924 . Communications interface  924  allows software and data to be transferred between computer system  900  and external devices. Examples of communications interface  924  may include a modem, a network interface (such as an Ethernet card), a communications port, a Personal Computer Memory Card International Association (PCMCIA) slot and card, etc. Software and data transferred via communications interface  924  are in the form of signals  928 , which may be electronic, electromagnetic, optical or other signals capable of being received by communications interface  924 . These signals  928  are provided to communications interface  924  via a communications path (e.g., channel)  926 . This path  926  carries signals  928  and may be implemented using wire or cable, fiber optics, a telephone line, a cellular link, a radio frequency (RF) link and/or other communications channels. In this document, the terms “computer program medium” and “computer usable medium” are used to refer generally to media such as a removable storage drive  980 , a hard disk installed in hard disk drive  970 , and signals  928 . These computer program products provide software to the computer system  900 . The invention is directed to such computer program products. 
     Computer programs (also referred to as computer control logic) are stored in main memory  908  and/or secondary memory  910 . Computer programs may also be received via communications interface  924 . Such computer programs, when executed, enable the computer system  900  to perform the features of the present invention, as discussed herein. In particular, the computer programs, when executed, enable the processor  910  to perform the features of the present invention. Accordingly, such computer programs represent controllers of the computer system  900 . 
     In an aspect where the invention is implemented using software, the software may be stored in a computer program product and loaded into computer system  900  using removable storage drive  914 , hard drive  912 , or communications interface  920 . The control logic (software), when executed by the processor  904 , causes the processor  904  to perform the functions of the invention as described herein. In another aspect, the invention is implemented primarily in hardware using, for example, hardware components, such as application specific integrated circuits (ASICs). Implementation of the hardware state machine so as to perform the functions described herein will be apparent to persons skilled in the relevant art(s). 
     In yet another aspect, the invention is implemented using a combination of both hardware and software. 
       FIG. 10  is a block diagram of various exemplary system components for providing communications with and between various components of the apparatus for measuring concentration, activity and content volume, in accordance with an aspect of the present invention.  FIG. 10  shows a communication system  1000  usable in accordance with the present invention. The communication system  1000  includes one or more accessors  1060 ,  1062  (also referred to interchangeably herein as one or more “users”) and one or more terminals  1042 ,  1066 . In one aspect, data for use in accordance with the present invention is, for example, input and/or accessed by accessors  1060 ,  1064  via terminals  1042 ,  1066 , such as personal computers (PCs), minicomputers, mainframe computers, microcomputers, telephonic devices, or wireless devices, such as personal digital assistants (“PDAs”) or a hand-held wireless devices coupled to a server  1043 , such as a PC, minicomputer, mainframe computer, microcomputer, or other device having a processor and a repository for data and/or connection to a repository for data, via, for example, a network  1044 , such as the Internet or an intranet, and couplings  1045 ,  1046 ,  1064 . The couplings  1045 ,  1046 ,  1064  include, for example, wired, wireless, or fiber optic links. In another aspect, the method and system of the present invention operate in a stand-alone environment, such as on a single terminal. 
     The previous description is provided to enable any person skilled in the art to fully understand the full scope of the disclosure. Modifications to the various configurations disclosed herein will be readily apparent to those skilled in the art. Thus, the claims are not intended to be limited to the various aspects of the disclosure described herein, but is to be accorded the full scope consistent with the language of claims, wherein reference to an element in the singular is not intended to mean “one and only one” unless specifically so stated, but rather “one or more.” Unless specifically stated otherwise, the term “some” refers to one or more. A claim that recites at least one of a combination of elements (e.g., “at least one of A, B, or C”) refers to one or more of the recited elements (e.g., A, or B, or C, or any combination thereof). All structural and functional equivalents to the elements of the various aspects described throughout this disclosure that are known or later come to be known to those of ordinary skill in the art are expressly incorporated herein by reference and are intended to be encompassed by the claims. Moreover, nothing disclosed herein is intended to be dedicated to the public regardless of whether such disclosure is explicitly recited in the claims. No claim element is to be construed under the provisions of 35 U.S.C. §112, sixth paragraph, unless the element is expressly recited using the phrase “means for” or, in the case of a method claim, the element is recited using the phrase “step for.” 
     While aspects of this invention have been described in conjunction with the example features outlined above, various alternatives, modifications, variations, improvements, and/or substantial equivalents, whether known or that are or may be presently unforeseen, may become apparent to those having at least ordinary skill in the art. Accordingly, the example aspects of the invention, as set forth above, are intended to be illustrative, not limiting. Various changes may be made without departing from the spirit and thereof. Therefore, aspects of the invention are intended to embrace all known or later-developed alternatives, modifications, variations, improvements, and/or substantial equivalents.