Patent Publication Number: US-2023146461-A1

Title: A stack of histology cassettes

Description:
FIELD OF THE INVENTION 
     The present invention relates to a stack of histology cassettes configured to be inserted into a hopper of a printer. 
     BACKGROUND 
     When biological tissue samples are collected, it is common to prepare the samples for analysis, e.g. for viewing under a microscope. One method of preparation is to process the tissue samples by treating the biological tissue using various fluids and then to embed each sample in an embedding medium, typically a block of paraffin wax. The various fluids used to treat the samples are typically referred to as reagents and may include: fixatives, alcohols and clearing agents (e.g. hydrocarbon solvents such as xylene). 
     Biological tissue samples are typically processed by a tissue processing apparatus, which may be an enclosed tissue processor for anatomical pathology. Prior to processing biological tissue in a tissue processing apparatus, the biological tissue is typically stored in a fixative such as Formaldehyde. Within a typical tissue processing apparatus, a biological tissue sample is first treated with alcohol, and then with a clearing agent (typically a hydrocarbon solvent, such as xylene). Finally, the tissue processing apparatus treats the biological tissue with paraffin wax (an embedding medium) so as to infiltrate and fill the biological tissue with the wax. It typically takes 14 hours for the tissue processing apparatus to complete this process. 
     Next, the biological tissue is embedded in a block of paraffin wax by a tissue embedding apparatus, which may be referred to as an “embedding centre”, in which the biological tissue (now filled with wax) is placed in a mould then filled with paraffin wax, which is rapidly cooled to form a solidified block of paraffin wax of predetermined shape and size (determined by the mould) containing the biological tissue. The predetermined shape and size of the block is chosen so that the solidified block is of a suitable shape and size to be used in a microtome, where the biological tissue can be cut into very fine slices that are suitable for use under a microscope. 
     Histology cassettes, often referred to simply as “cassettes”, are used to hold biological tissue samples during processing and embedding of the samples. 
     Histology cassettes are typically marked with data for use in identifying and tracking a sample held by the cassette whilst the cassette is in use. Such data is referred to as “cassette data” herein. The cassette data may include a visual machine-readable identifier such as a barcode (e.g. a 1D or 2D barcode). The cassette data may include a patient name which identifies a patient who provided a sample held by the cassette. The cassette data may include a string of letters and/or numbers which uniquely identifies the sample. The cassette data may include details of the lab which obtained the sample. 
     In most modern devices, histology cassettes are marked with cassette data by a printer, which may be referred to as a histology cassette printer, but is herein referred to simply as a “printer”. 
     A typical printer includes a hopper configured to hold a stack of histology cassettes, wherein the printer is configured to print data onto each cassette held by the hopper, e.g. based on a signal from a computer. 
     Typically, a hopper will hold 30 or more cassettes, e.g. 60-80 cassettes. Typically cassette data is printed by the printer directly onto a material from which the cassette itself is made. But it is also possible for a printer to print cassette data onto a label applied to the cassette. For practical reasons, cassette data is usually printed onto a cassette before holding a sample in the cassette. 
     Histology cassettes can be supplied in a number of different packaging arrangements to feed into a printer. The packaging arrangement is usually dependent on the printer used. In some cases, histology cassettes are hand fed into a printer loose, i.e. one at a time. However, this is burdensome and can lead to cassettes becoming stuck in a hopper of the printer. In other cases, a stack of histology cassettes are loaded together into (e.g. a hopper of) a printer. 
     It is known for a stack of histology cassettes to be taped together, primarily to facilitate easier loading the cassettes into a printer. 
     For example, EP1238706A2 and U.S. Pat. No. 7,507,379B2 disclose arrangements in which an adhesive tape adheres to one side of a stack of histology cassettes. The present inventors have observed that a stack of histology cassettes bound together in this way is unstable (e.g. floppy) and difficult to insert into a hopper of a printer (particularly one handed). 
     US 2015/0241325A1 and EP2881175A1 disclose arrangements in which a stack of histology cassettes are held together by a non-adhesive strip which passes through an aperture in each of the histology cassettes. The present inventors have observed that a stack of histology cassettes bound together in this way can still be a slightly unstable (e.g. floppy) and difficult to insert into a hopper of a printer (particularly one handed). Moreover, the present inventors have observed that disconnecting the histology cassettes by pulling out the non-adhesive strip from the cassettes requires considerable force, which might be challenging for some users. Moreover, these arrangements only work with histology cassettes which include a suitable aperture through which the non-adhesive strip can be inserted—such apertures are not present in many histology cassettes. 
     The present invention has been devised in light of the above considerations. 
     SUMMARY OF THE INVENTION 
     A first aspect of the invention provides:
         A stack of histology cassettes configured to be inserted into a hopper of a printer;   wherein each histology cassette in the stack includes a bottom face, a top face opposite the bottom face, a front face, a rear face opposite the front face, a first lateral face and a second lateral face opposite the first lateral face, wherein the top face of the histology cassette is open to allow a sample to be received within the histology cassette;   wherein the histology cassettes have substantially the same orientation within the stack;   wherein the histology cassettes in the stack are arranged with a first histology cassette at the bottom of a stack, and with each subsequent histology cassette in the stack up to a last histology cassette in the stack being arranged with its bottom face being positioned on the top face of a preceding histology cassette in the stack;   wherein the histology cassettes in the stack are held together by a length of tape which loops around the entire stack of histology cassettes;   wherein the length of tape includes a first fixing region and a second fixing region wherein the first fixing region overlaps and adheres to the second fixing region;   wherein the length of tape includes a release region at an end of the length of tape, the release region being configured to be pulled by a user after the stack of histology cassettes has been inserted into a hopper of a printer so as to release the first fixing region from the second fixing region thereby releasing the histology cassettes within the hopper of the printer.       

     By looping the tape around the entire stack of histology cassettes, the cassettes in the stack can be tightly held together in a more stable fashion and thus easily manipulated with one hand. Yet the cassettes can be easily released from being held together after being inserted into the printer simply by pulling on the release region. The release region may herein be referred to as a release tab. 
     Preferably, the release region is at a first end of the length of tape, wherein the first fixing region is closer to the first end of the length of tape than to a second end of the length of tape opposite to the first end of the length of tape. Preferably, the release region and the first fixing region are on the same side of the stack as each other. 
     These features help to facilitate easy release of the first fixing region from the second fixing region by pulling on the release region. 
     The second fixing region may be closer to the second end of the length of tape than the first end of the length of tape. But this is not a requirement, since the length of tape could loop around the entire stack of histology cassettes, such that the first and second fixing regions are both closer to the first end of the length of tape. 
     Preferably, the length of tape holds the histology cassettes together, preferably rigidly together, by applying pressure to the histology cassettes (e.g. by tightly wrapping around the stack of histology cassettes), more preferably without the length of tape adhering to the histology cassettes. These features help to facilitate the releasing of the cassettes in the printer, without leaving a deposit of sticky material (e.g. a sticky film of glue) on the cassettes. 
     In some examples, the length of tape is configured so that the release region projects outwardly from the stack of histology cassettes. This may be achieved, for example, by bending the length of tape so that the release region projects outwardly from the stack of histology cassettes. This may help a user locate the release region, prior to pulling on it. 
     A length axis may be defined with respect to each histology cassette as extending from the rear face to the front face of the cassette. A lateral axis may be defined with respect to each histology cassette as extending from the first lateral face to the second lateral face of the cassette. A depth axis may be defined with respect to each histology cassette as extending from the bottom face to the top face of the cassette. The length, lateral and depth axes are preferably mutually orthogonal. 
     The cassette is preferably longer in the direction of the length axis of the cassette than it is wide in the direction of the lateral axis of the cassette. The cassette is preferably wider in the direction of the lateral axis of the cassette than it is deep in the depth direction of the cassette. 
     The stack may have a front face formed by the front faces of the cassettes in the stack, a rear face formed by the rear faces of the cassettes in the stack, a first lateral face formed by the first lateral faces of the cassettes in the stack, a second lateral face formed by the second lateral faces of the cassettes in the stack, a bottom face formed by the bottom face of the first cassette in the stack, and a top face formed by the top face of the last cassette in the stack. 
     The length of tape looped around the entire stack of histology cassettes preferably extends along the top face, first lateral face, bottom face and second lateral face of the stack. This is preferable to the length of tape looping around the stack in other configurations since it helps to facilitate easy insertion into a hopper of a printer. For example, looping the tape around the stack in this configuration allows for use of a tape that is wider, compared with a configuration in which the tape extends along the top, front, bottom and rear faces of the stack (where the cassettes in the stack are longer in the direction of the length axis of the cassette than they are wide in the direction of the lateral axis of the cassette—see above). 
     However, in other embodiments, it would be possible for the tape to instead extend along the top, front, bottom and rear faces of the stack. 
     Embodiments in which the tape extends along the front, first lateral, rear and second lateral faces of the stack may also be possible, depending on the shape of the cassettes, and configuration of the printer. 
     A second aspect of the invention may provide a histology cassette system including:
         a stack of histology cassettes according to the first aspect of the invention;   a printer including a hopper configured to receive the stack of histology cassettes.       

     The hopper can be considered as any element configured to receive a stack of histology cassettes, and may have a tubular form. The hopper may be integral with, or detachable from the printer. The hopper may alternatively be referred to as a “magazine”, and the terms “hopper” and “magazine” may be used interchangeably herein. The hopper may hold 30 or more cassettes. 
     The printer may be configured to print data onto each cassette held by the hopper, e.g. based on a signal from a computer. The printer may be configured to sequentially print data onto each cassette (i.e. print on each cassette in turn), starting with the first cassette. 
     The printer may be configured to print cassette data onto each cassette by printing directly onto a material from which the cassette itself is made. But it is also possible for the printer to be configured to print cassette data onto each cassette by printing onto a label applied to the cassette. For practical reasons, the printer may be configured to print cassette data onto each cassette before holding a sample in the cassette. 
     The hopper may include a front wall, rear wall, first lateral wall and second lateral wall which define a passage configured to receive the stack of histology cassettes such that when the stack of histology cassettes is inserted into the hopper, the front wall of the stack faces the front wall of the hopper, the rear wall of the stack faces the rear wall of the hopper, the first lateral wall of the stack faces the first lateral wall of the hopper and the second lateral wall of the stack faces the second lateral wall of the hopper. 
     The printer may be configured to receive the stack of histology cassettes with the bottom face of the stack of histology cassettes being inserted first into the passage defined by the front, rear, first lateral and second lateral walls of the hopper. Other hopper arrangements are possible. 
     One of the walls of the hopper (i.e. one of the front wall, rear wall, first lateral wall and second lateral wall), preferably one of the lateral walls of the hopper (i.e. the first or second lateral wall), may include a slot extending in the direction of the passage defined by the walls, to allow manipulation of the cassettes within the hopper. 
     The tape which loops around the entire stack of cassettes may be configured such that the release region of the tape is accessible via the slot (e.g. by the tape being aligned with this slot such that a user can reach the release region with their fingers via the slot) when the stack of cassettes has been inserted into the hopper, so as to facilitate easy separation of the cassettes within the hopper, i.e. such that the release tab can be pulled by a user after the stack of cassettes has been inserted into the hopper. 
     The tape which loops around the entire stack of cassettes may be configured such that the release region of the tape is visible via the slot (e.g. by being aligned with this slot such that a user can see the release region) when the stack of cassettes has been inserted into the hopper, again so as to facilitate easy separation of the cassettes within the hopper. 
     The release tab may also be configured to align with this slot, when the stack of cassettes has been inserted into the hopper, so as to facilitate easy separation of the cassettes within the hopper, i.e. such that the release tab can be pulled by a user after the stack of cassettes has been inserted into the hopper. 
     The invention includes the combination of the aspects and preferred features described except where such a combination is clearly impermissible or expressly avoided. 
    
    
     
       SUMMARY OF THE FIGURES 
       Examples illustrating the principles of the invention will now be discussed with reference to the accompanying figures in which: 
         FIG.  1    is a perspective view of a histology cassette. 
         FIG.  2    is a perspective view of a stack of histology cassettes. 
         FIG.  3    is a perspective view of a hopper configured to receive a stack of histology cassettes. 
         FIGS.  4 ( a )-( e )  show steps in the removal of a length of tape from around a stack of histology cassettes. 
         FIG.  5    is a perspective view of a further example of a stack of histology cassettes. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     Aspects and embodiments of the present invention will now be discussed with reference to the accompanying figures. Further aspects and embodiments will be apparent to those skilled in the art. All documents mentioned in this text are incorporated herein by reference. 
       FIG.  1    is a perspective view of a histology cassette  101  with histology cassette data  108  printed on the histology cassette  101 . 
     The histology cassette  101  as shown in  FIG.  1    includes a top face  102 , a bottom face  103  opposite the top face  102 , a front face  104 , a rear face  105  opposite the front face  104 , a first lateral face  106  and a second lateral face  107  opposite the first lateral face  106 . The top face  102  of the histology cassette  101  is open. 
     On the front face  104  of the histology cassette  101  is cassette data  108 . The cassette data  108  includes a visual machine-readable identifier  109 , a patient name  110  (in this case “patient X”) and a string of letters and numbers  111  (in this case “A 1 ”). 
     A length axis “le” may be defined with respect to the histology cassette  101  as extending from the rear face  105  to the front face  104  of the histology cassette  101 . A lateral axis “la” may be defined with respect to the histology cassette  101  as extending from the first lateral face  106  to the second lateral face  107  of the histology cassette  101 . A depth axis “d” may be defined with respect to the histology cassette  101  as extending from the bottom face  103  to the top face  102  of the histology cassette  101 . The length, lateral and depth axes are mutually orthogonal. 
     The histology cassette  101  as shown in  FIG.  1    is longer in the direction of the length axis of the histology cassette  101  than it is wide in the direction of the lateral axis of the histology cassette  101 . The histology cassette  101  is wider in the direction of the lateral axis of the histology cassette  101  than it is deep in the depth direction of the histology cassette  101 . 
     In use, the top face  102  of the histology cassette  101  is open to allow a biological tissue sample (which may be referred to as a “sample” herein) to be received within the histology cassette  101 . The histology cassette  101  then holds the sample during the processing and embedding of the sample. 
     The histology cassette data  108  identifies and tracks a sample held by the histology cassette  101  whilst the histology cassette  101  is in use. The patient name  110  identifies a patient who provided a sample held by the histology cassette  101 . The string of letters and numbers  111  in the cassette data  108  uniquely identify the sample. 
       FIG.  2    shows a stack  250  of histology cassettes  201  according to an example of the present invention. 
     Each histology cassette  201  in the stack  250  may have the same configuration as the histology cassette  101  shown in  FIG.  1    prior to the printing of cassette data  108  by a printer onto the front face  104  of each histology cassette  201  in the stack  250  of histology cassettes  201 . The stack  250  of histology cassettes  201  shown in  FIG.  2    has a length of tape  220  looped around the entire stack  250  of histology cassettes  201 . 
     Each histology cassette  201  in the stack  250  has substantially the same orientation within the stack  250 . The histology cassettes  201  in the stack  250  are arranged with a first histology cassette  221  at the bottom of a stack  250 . Each subsequent histology cassette in the stack  250 , up to a last histology cassette  222  in the stack  250 , is arranged with its bottom face positioned on the top face of a preceding histology cassette in the stack  250 . 
     As discussed in relation to the histology cassette  101  shown to  FIG.  1   , a length axis “le” may be defined as extending from the rear face to the front face of each histology cassette  201 . A lateral axis “la” may be defined as extending from the first lateral face to the second lateral face of each histology cassette  201 . A depth axis “d” may be defined as extending from the bottom face to the top face of each histology cassette  201 . The length, lateral and depth axes are mutually orthogonal. 
     Each histology cassette  201  in the stack  250  is longer in the direction of the length axis than it is wide in the direction of the lateral axis. Each histology cassette  201  in the stack  250  is wider in the direction of the lateral than it is deep in the depth direction. 
     The stack  250  of histology cassettes  201  has a front face  223 , a rear face  224 , a first lateral face  225 , a second lateral face  226 , a top face  227  and a bottom face  228 . The front face  223  is formed by the front faces of the histology cassettes  201  in the stack  250 . The rear face  224  is formed by the rear faces of the histology cassettes  201  in the stack  250 . The first lateral face  225  is formed by the first lateral faces of the histology cassettes  201  in the stack  250 . The second lateral face  226  is formed by the second lateral faces of the histology cassettes  201  in the stack  250 . The top face  227  is formed by the top face  227  of the last histology cassette  222  in the stack  250 . The bottom face  228  is formed by the bottom face of the first histology cassette  221  in the stack  250 . 
     The length of tape  220  has a first end  433  and a second end  434  (shown in later figures). The first end  433  of the length of tape  220  is opposite the second end  434  of the length of tape  220 . The length of tape  220  is looped around the entire stack  250  of histology cassettes  201 . The loop of tape  220  extends along the top face  227 , the first lateral face  225 , the bottom face  228  and the second lateral face  226  of the stack  250  of histological cassettes  201 . The length of tape  220  includes a first fixing region  230  and a second fixing region  431  (shown in later figures). Only the first fixing region  230  is visible because the second fixing region  431  is underneath the first fixing region  230 . The second fixing region  431  can be seen in  FIG.  4 ( b ) . The first fixing region  230  is closer to the first end  433  of the length of tape  220  than to the second end  434  of the length of tape  220 . The first fixing region  230  overlaps and adheres to the second fixing region  431 . The length of tape  220  also includes a release region  232 . The release region  232  may be referred to as the release tab. The release region  232  is at the first end  433  of the length of tape  220  and the release region  232  and the first fixing region  230  are on the same side of the stack  250  of histology cassettes  201  as each other. The release region  232  is closer to the first end  433  of the length of tape  220  than the first fixing region  230  is to the first end  433  of the length of tape  220 . 
     In this example, the length of tape  220  rigidly holds together the stack  250  histology cassettes  201  by applying pressure to the stack  250  of histology cassettes  201 . In this example, this rigid holding together of the histology cassettes  201  is achieved by the length of tape  220  being tightly looped around the stack  250  of histology cassettes  201  without the length of tape  220  adhering to the histology cassettes  201 . 
     The release region  232  is configured to be pulled by the user after the stack  250  of histology cassettes  201  has been inserted into a hopper  375  (shown in later figures) of a histology cassette  201  printer so as to release the first fixing region  230  from the second fixing region  431  thereby releasing the histology cassettes  201  within the hopper  375  of the histology cassette  201  printer. 
     By rigidly holding the stack  250  of histology cassettes  201  together, the stack  250  of histology cassettes  201  is able to be moved without the histology cassettes  201  flopping around. This allows for a stack  250  of histology cassettes  201  to be inserted into a hopper  375  of a histology cassette  201  printer more easily (especially when only using one hand to insert the histology cassettes  201  into the printer). 
       FIG.  3    shows a perspective view of a hopper  375  configured to receive the stack  250  of histology cassettes  201  shown in  FIG.  2   . 
     The hopper  375  has a front wall  383 , a rear wall  384  opposite the front wall  383 , a first lateral wall  385 , and a second lateral wall  386  opposite the first lateral wall  385 . The front wall  383 , the rear wall  384 , the first lateral wall  385  and the second lateral wall  386  define a passage. The passage has a first end  387  which is open and a second end  388  opposite the first open end  387 . The first lateral wall  385  has a slot  391  extending in the direction of the passage defined by the walls  383 ,  384 ,  385 ,  386 . The slot  391  extends from the first end  387  of the hopper  375  to the second end  388  of the hopper  375 . 
     A length axis extends from the rear wall  384  to the front wall  383  of the hopper  375 . A lateral axis extends from the first lateral wall  385  to the second lateral wall  386  of the hopper  375 . A depth axis extends from the first end  387  of the passage to the second end  388  of the passage. The length, lateral and depth axes are mutually orthogonal. The hopper  375  is longer in the length axis than it is wide in the direction of the lateral axis. The hopper  375  is deeper in the direction of the depth axis than it is wide in the lateral axis. The hopper  375  is deeper in the direction of the depth axis than it is long in the length axis. 
     At the second end  387  of the hopper  375  is a histology cassette  201  support  389 . The histology cassette  201  support  389  has a support surface  890  which is perpendicular to the front wall  383 , rear wall  384 , first lateral wall  385  and second lateral wall  386  of the hopper  375 . The histology cassette  201  support  389  is attached to the rear wall  384  of the hopper  375 . 
       FIGS.  4 ( a )-( e )  shows a method of inserting the stack  250  of histology cassettes  201  (shown in  FIG.  2   ) into the hopper  375  (shown in  FIG.  3   ). 
     As shown in  FIG.  4 ( a ) , the stack  250  of histology cassettes  201  has been inserted into (and therefore received by) the hopper  375 . The stack  250  of histology cassettes  201  has been inserted into the hopper  375  with the bottom face  228  of the stack  250  of histology cassettes  201  being inserted first into the first open end  387  of the hopper  375 . Having been inserted into the hopper  375 , the stack  250  of histology cassettes  201  is supported by the support surface  390  of the histology cassette  201  support  389 . 
     The front face  223  of the stack  250  of histology cassettes  201  faces the front wall  383  of the hopper  375 , the rear face  224  of the stack  250  of histology cassettes  201  faces the rear wall  384  of the hopper  375 , the first lateral face  225  of the stack  250  of the histology cassettes  201  faces the first lateral wall  385  of the hopper  375  and the second lateral face  226  of the stack  250  of the histology cassettes  201  faces the second lateral wall  386  of the hopper  375 . The bottom face  228  of the stack  250  of histology cassettes  201  is in contact with the support surface  390  of the histology cassette support  389 . 
     The length of tape  220  that loops round the entire stack  250  of histology cassettes  201  is aligned with the slot  391  in the first lateral face  385  of the hopper  375 . 
     The release region  232  of the length of tape  220  is aligned with the slot  391  in the first lateral wall  385  of the hopper  375 . The release region  232  of the length of tape  220  lies parallel to the slot  391  in the first lateral wall  385  of the hopper  375 . The release region  232  does not project outwardly from the stack  250  of histology cassettes  201 . The first fixing region  230  and the second fixing region  431  of the length of tape  220  are aligned with the slot  391  in the first lateral wall  385  of the hopper  375 . The first fixing region  230  and the second fixing region  431  of the length of tape  220  are parallel to the slot  391 . 
     Note that because the tape  220  is aligned with the slot  391 , this allows for easy separation of the cassettes  201  within the hopper  375  because the release tab  232  can be pulled by a user after the stack  250  of cassettes  201  has been inserted into the hopper  375 . In use, a user pulls on the release region  232  of the tape  220 , which causes the first fixing region  230  to begin to detach from the second fixing region  431 , as shown in  FIG.  4 ( b ) . 
     Next, as the user continues to pull upwardly on the release region  432 , the first fixing region  230  becomes completely detached from the second fixing region  431 , as shown in  FIG.  4 ( b ) , and the second end  434  of the length of tape  220  falls out of the hopper  375 , as shown in  FIG.  4 ( c ) . 
     Next, the user continues to pull on the release region  232  so that the histology cassettes  201  are released in the hopper  375  as shown in  FIG.  4 ( d ) . 
     Finally, the tape  220  is removed, leaving behind the released histology cassettes  201  in the hopper  375 , as shown in  FIG.  4 ( e ) . 
     With the histology cassettes  201  now released, a printer may subsequently take each histology cassette  201  in turn (starting with the first histology cassette  221 ) in order to print cassette data  108  onto each histology cassette  201  in the hopper  375 . 
       FIG.  5    shows a stack  550  of histology cassettes  501  with a length of tape  520  looped around the entire stack  550  of histology cassettes  501 , where the stack  550  of histology cassettes  501  is the same as shown in  FIG.  2   . In this example the release region  532  projects outwardly from the stack  550  of histology cassettes  501 . This helps a user locate the release region  532 , prior to pulling on it. In use, a user pulls the release region  532  of the length of tape  520  to remove the length of tape  520  from around the stack  550  of histology cassettes  501 . 
     In some examples (not shown), the length of tape may be looped around the stack of histology cassettes such that it extends along the top, front, bottom and rear faces of the stack. 
     Alternative, it may be possible for the length of tape looped around the stack of histology cassettes to extend along the front, first lateral, rear and second lateral faces of the stack, depending on the shape of the cassettes, and configuration of the printer. 
     The features disclosed in the foregoing description, or in the following claims, or in the accompanying drawings, expressed in their specific forms or in terms of a means for performing the disclosed function, or a method or process for obtaining the disclosed results, as appropriate, may, separately, or in any combination of such features, be utilised for realising the invention in diverse forms thereof. 
     While the invention has been described in conjunction with the exemplary embodiments described above, many equivalent modifications and variations will be apparent to those skilled in the art when given this disclosure. Accordingly, the exemplary embodiments of the invention set forth above are considered to be illustrative and not limiting. Various changes to the described embodiments may be made without departing from the spirit and scope of the invention. 
     For the avoidance of any doubt, any theoretical explanations provided herein are provided for the purposes of improving the understanding of a reader. The inventors do not wish to be bound by any of these theoretical explanations. 
     Any section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described. 
     Throughout this specification, including the claims which follow, unless the context requires otherwise, the word “comprise” and “include”, and variations such as “comprises”, “comprising”, and “including” will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps. 
     It must be noted that, as used in the specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Ranges may be expressed herein as from “about” one particular value, and/or to “about” another particular value. When such a range is expressed, another embodiment includes from the one particular value and/or to the other particular value. Similarly, when values are expressed as approximations, by the use of the antecedent “about,” it will be understood that the particular value forms another embodiment. The term “about” in relation to a numerical value is optional and means for example +/−10%.