Multi-lumen instrument guide

This document discusses, among other things, a method of manufacture including a mold having at least one pin, and surrounding the pin with a hardenable material to form a first guide layer. The mold and pin are removed from the resulting first guide layer, to define a substantially untapered first instrument passage that corresponds to the geometry of the pin. Optionally, the first instrument passage includes at least five substantially untapered channels including a central channel. The first instrument passage is aligned with a substantially untapered second instrument passage of a stacked second guide layer. In a further example, the first and second guide layers are coupled to a guide coupler that cooperatively aligns the first and second instrument passages. The guide layers can be used with a trajectory guide for image guided surgery.

RELATED APPLICATIONS

This application is related to U.S. patent application Ser. No. 11/005,607, filed on Dec. 4, 2004, entitled “INSTRUMENT GUIDING STAGE APPARATUS AND METHOD FOR USING SAME,” the disclosure of which is incorporated herein by reference in its entirety.

This application is related to U.S. patent application Ser. No. 10/370,090, filed on Feb. 20, 2003, entitled “TRAJECTORY GUIDE WITH ANGLED OR PATTERNED GUIDE LUMENS OR HEIGHT ADJUSTMENT,” the disclosure of which is incorporated herein by reference in its entirety.

TECHNICAL FIELD

This document relates generally to guiding instruments and in particular, but not by way of limitation, to a multi-lumen insert, such as for use with a trajectory guide for surgically guiding instruments.

BACKGROUND

Neurosurgery sometimes involves inserting an instrument through a burr hole or other entry portal into a subject's brain toward a target region of the brain. Because of the precision needed to reach the target, while avoiding nearby structures that are often critical to brain function, precise guidance devices and techniques are needed. In one such technique a multi-lumen instrument guide is included within a trajectory guide mounted to the skull. An instrument is inserted through a guide lumen of the instrument guide, which steers it toward the target.

DETAILED DESCRIPTION

In order to accurately plunge an instrument into the brain, the instrument typically must be aligned to and guided on the proper trajectory toward the target. The better an instrument is aligned to and held on the ideal trajectory, the more accurate will be the guidance and placement of the instrument at the target.

Many surgical instruments are long, thin, slightly flexible tubes or rods. Guiding such an instrument, therefore, typically involves guiding a round tube in a round guide hole (also referred to as a guide lumen) as the tube passes through the hole (and beyond, toward the target). The guided instrument should remain as nearly concentric to and as nearly parallel to the guide lumen as possible. This concentricity and parallelism should extend even at relatively long distances from the exit of the guide lumen. Stated another way, the instrument's concentricity and parallelism to the ideal trajectory should be adequate at a specified target distance from the guiding apparatus.

Among the characteristics that will improve tubular instrument guidance are: (1) a tighter fit between an inner diameter of the guide lumen and an outer diameter of the tubular instrument; (2) a longer axial engagement or guidance of the tubular instrument with the guide lumen (i.e., a long-bore in the guide lumen); (3) a shorter distance from the guide lumen exit to the target (i.e., placing the guiding apparatus closer to the brain or other target); and/or (4) a stiffer instrument being guided toward the target.

However, manufacturing long, small-bore holes, such as needed for instrument guidance, can be difficult and costly, particularly where a pattern of multiple small-bore holes is required, instead of a single small-bore hole, and even more particularly where the multiple small-bore holes must be closely spaced to each other. Small-bore holes are typically made by techniques including: drilling (such as normal machining, laser drilling, electrical discharge machining (EDM), or the like); molding material around a pin, then removing the pin; or extruding a tube with an inside diameter equal to that of the desired small-bore hole.

Drilled holes often have a practical limit on the obtainable depth. An adequately long, straight, drilled hole suitable for accurate instrument guidance is often difficult or impossible to obtain. Although exotic methods such as laser drilling or EDM may work, their costs are typically high and the materials with which they may be used are typically limited. Even if a single long small-bore hole can be drilled, for example, drilling another nearby hole can be very difficult because the drill bit may wander or break through the material separating the adjacent small-bore holes.

Molding long holes is possible. However, molding draft (i.e., taper) is usually required, especially for long holes. Even with such molding draft, as a practical matter, molded small-bore holes are limited to a modest length. The pins that form such holes are typically too weak and flexible when they are made too long. Moreover, drafted holes will affect the tightness of fit between the instrument and the hole, making it difficult for a drafted molded hole to provide adequate instrument guidance.

An extruded tube may alternatively be inserted as a liner in a larger diameter hole to more snugly guide the tubular instrument. Alternatively, the wider end of the tapered small-bore hole could be plugged with a sleeve to narrow its effective inner diameter. However, each of these techniques proves difficult when multiple closely-spaced small-bore holes are needed. The material separating the closely-spaced holes becomes too thin and frangible.

Another technique would be to align two shorter, separated multi-lumen guides. However, aligning the guides to each other is difficult, and the user must spear the instrument through a guide lumen not only at the proximal guide, but at the distal guide as well. This can be awkward for the user, and it is possible that the instrument could enter the wrong guide lumen in the more distal guide, thereby deflecting along the wrong trajectory into the brain and away from the desired target.

Drilling, molding, extrusion, and other techniques, therefore, all present problems when multiple closely-spaced small-bore holes are needed. Opting for a shorter bore instrument guide, however, will compromise the accuracy with which the instrument can be guided toward the target.

Among other things, the present inventors have recognized difficulties with ordinary manufacturing techniques to construct multi-lumen instrument guides with tight tolerance passages to provide accurate targeting of instruments. The present inventors have also recognized an unmet need for reducing trauma to the brain through enhanced flexibility in instrument targeting where the center to center distance of passages within multi-lumen instrument guides is reduced (i.e., instruments are able to accurately traverse around blood vessels, vital tissues, and the like).

FIG. 1is an exploded perspective view of an example of an instrument guide100. The instrument guide100includes at least two guide layers102. In the example shown inFIG. 1, the instrument guide100includes ten guide layers102. Optionally, the instrument guide100includes additional guide layer102or fewer guide layers102. In one example, the instrument guide100includes a guide coupler104carrying the guide layers102. In one example, the inner surface106of the guide coupler104defines a guide layer lumen108. The guide layer lumen108is cylindrical in one example. In another example, the guide layer lumen108has a different geometry, for example a rectangle, triangle, oval or the like. Optionally, the inner surface106is sized and shaped to snugly retain the guide layers102. In another example, one or more ridges107extend from the inner surface106into the guide layer lumen108. In one example, the ridges107are disposed along the inner surface106approximately every 90 degrees. In another example, the ridges107are disposed at lesser or greater increments. Optionally, the ridges107have a triangular cross-sectional geometry. In an example, the base of a ridge107extends from the inner surface106to an edge within the guide layer lumen108.

In an example, the guide coupler104includes an upper portion110and a lower portion112. In one example, the upper portion110has a smaller outer perimeter than the lower portion112. In other words, the upper portion110is narrower than the lower portion112. In the example ofFIG. 1, the upper portion110is parallel to a longitudinal center axis111of the guide coupler104and offset from the longitudinal center axis111. In other words, the longitudinal center axis113of the upper portion110is offset from the longitudinal center axis111of the guide coupler104. In another example, the upper portion110longitudinal center axis113is aligned with the longitudinal center axis111of the guide coupler104.

The guide coupler upper portion110optionally includes keys114disposed around the outer perimeter of the upper portion110. In one example, the keys114are disposed around an outer perimeter of the upper portion110at 90 degree increments. The outer perimeter of the upper portion110, in an example, includes a first recess116. In the example shown inFIG. 1, the first recess116extends circumferentially around the upper portion110. In another example, the first recess116extends part way around the upper portion110. In yet another example, a second recess118extends around the lower portion112. Optionally, the second recess118extends part way around the lower portion112. A flange120is interposed between the upper portion110and lower portion112. In an example, the flange120has an outer perimeter greater than that of the upper portion110and lower portion112. In another example, the flange120extends part way around the guide coupler104.

In one example, the guide coupler104and guide layer102are constructed with hardenable materials such as, but not limited to, polycarbonate, injection molded plastics, epoxies and the like. In another example, the guide coupler104and guide layer102are made, at least partially, with a thermoplastic having polyamide with the trade name Grilamid®, which is registered to EMS-Grivory. In still another example, the guide coupler104and guide layer102are made with any biocompatible material. Optionally, the guide coupler104and guide layer102are constructed with differing materials.

FIG. 2is a perspective view of a guide layer102. In one example, the outer perimeter200of the guide layer102has a substantially cylindrical geometry and the guide layer102has a diameter of approximately 0.4 inches. In another example, the outer perimeter200has a different geometry, for example rectangular, triangular, ovular or the like. In an example, the outer perimeter200is sized and shaped to snugly fit within the inner surface106of the guide coupler104. In an example, the guide layer102includes grooves202disposed around the outer perimeter200. In the example shown inFIG. 2, four grooves202are disposed around the guide layer102. Optionally, fewer or additional grooves202are disposed around the guide layer102. In one example, the grooves200extend from an upper surface of the guide layer102to a lower surface. In another example, the grooves202are disposed around the guide layer102at approximately 90 degree increments. In yet another example, the grooves202are disposed at differing increments. In one option, the grooves202have a corresponding geometry to ridges107. In an example, the grooves have a triangular geometry. In another example, the ridges107are sized and shaped to snugly fit within the grooves202. The ridges107and grooves202cooperatively align different stacked guide layers102with the guide coupler104, and with each other, when the guide layers102are disposed within the guide layer lumen108. In still another example, ridges extend from the guide layers102into grooves disposed on the inner surface106of the guide coupler104. Optionally, the guide layers and the guide coupler have non-circular geometries (e.g., triangular, ovular, and the like) that facilitate alignment without the ridges and grooves.

The guide layer102optionally further includes at least one substantially untapered instrument passage204. The instrument passage204extends through the guide layer102and is non-threaded. In another example, the instrument passage204is a channel disposed on the guide layer102. In yet another example, the instrument passage204is a lumen disposed within the guide layer102. The longitudinal center axis205of the instrument passage204, is optionally coincident with the longitudinal center axis of the guide layer102. In another example, the longitudinal center axis205of the instrument passage204is parallel to but offset from the longitudinal center axis205of the guide layer102. In still another example, the instrument passage204longitudinal center axis205is not parallel with the longitudinal center axis of the guide layer102. In other words the instrument passage204is at an angle to the longitudinal center axis of the guide layer102. The instrument passage204has an inner diameter that is circular, elliptical, rounded, chamfered or the like, in one example.

In the example shown inFIG. 2, the instrument passage204includes five substantially untapered channels206A-E. In other words, the diameter of the approximately cylindrical channels206A-E remains substantially unchanged throughout the guide layer102, and throughout the middle additional stacked guide layers102. The substantially untapered characteristic of the channels206A-E ensures there is a tight clearance between instruments and the guide layers102. The substantially untapered channels206A-E, in one example, include a slight taper so at least a portion of the inner diameter of the channels206A-E provides a tight tolerance slidable coupling with an instrument. In an example, the channels206A-E are interconnected, as shown inFIG. 2. A common inner surface of instrument passage204defines the channels206A-E. In another example, channels206A-E are separate and distinct cylindrical lumens rather than being interconnected. In an example, the channels206A-D are disposed around substantially centered channel206E, such as at 90 degree increments approximately. This can be conceptualized as a North-South-East-West configuration about the centered channel206E. Optionally, some or all of channels206A-E are not interconnected. In one example, additional channels are provided in guide layer102. In still another example, the channels are disposed within guide layer102in a different pattern, for example a three by three matrix of channels, or the like. In yet another example, the instrument passage includes two or more channels disposed in a pattern. Referring again to the example shown inFIG. 2, each of the channels206A-E, optionally have a diameter of about 0.075 inches and are spaced from the other adjacent channels206A-E about 0.0787 inches center-to-center.

In the example ofFIG. 1, the instrument guide100includes multiple guide layers102stacked within guide coupler104. The guide layers102are disposed within guide layer lumen108, such as with the ridges of the guide coupler104disposed within grooves202of the guide layers102. This retains the individual guide layers102within the guide layer lumen108in a desired orientation. In other words, the ridges107and corresponding grooves202align the instrument passage204of one guide layer102with the instrument passages204of the other guide layers102disposed within the guide layer lumen108. Further, the channels206A-E of one guide layer102are also aligned with the channels206A-E of the other guide layers102through the cooperative relationship of the ridges107and grooves202. The channels206A-E thus define substantially untapered passages extending through the stacked guide layers102. In other words, the channels206A-E are sized and shaped to create tight tolerance passages that accurately maintain a consistent diameter through the entire stack of guide layers102. This ensures accurate tracking of instruments snugly coupled to the guide layers102within channels206A-E and fed through the instrument guide100.

The substantially untapered channels206A-E of the guide layers102, shown inFIG. 1, are symmetrical in the example described above. As a result, the guide layers102can be assembled in any orientation in which they will fit into the guide layer lumen108(e.g. by disposing the ridges10within the grooves202) and define the substantially untapered passages extending through the stacked guide layers102. The guide layers102, in one example, are substantially identical and interchangeable. Interchangeable guide layers102expedite assembly of the instrument guide100as the guide layers are stacked in any order or orientation (for instance, top side down or bottom side up) within the guide coupler104.

In another example, the guide layers102include channels206A-E that have a slight taper (described above). When the guide layers102are stacked in the guide coupler104the channels206A-E provide substantially untapered passages. The effect of the greater clearance between the channels206A-E and an instrument caused by the slight taper is lessened as at least a portion of the inner diameters of the channels206A-E provides a tight tolerance slidable coupling to instruments. Coupling the guide layers102together further overcomes the effect of the slight taper as each elongated passage includes multiple tight tolerance inner diameter portions that slidably couple with the instruments. As a result, channels206A-E provide substantially untapered passages when the guide layers102are stacked.

FIG. 3shows a perspective view of an instrument guide301coupled to a trajectory alignment assembly300. The instrument guide301ofFIG. 3is similar to the instrument guide100. However, the instrument guide301includes an instrument passage204with a centered channel206E that is substantially coincident with a longitudinal axis of the instrument guide301. Trajectory alignment assembly300includes a base ring302. In one example, the base ring302is coupled to an instrument immobilizer or other fixture that is disposed around a burr hole in a patient's skull. In another example, the base ring302is coupled to the skull or another portion of the body. A rotatable base304is coupled to the base ring302and operable to rotate around the base ring302. A saddle slide306is disposed on an arcuate top portion of the rotatable base304. In an example, the saddle slide306is slidably coupled to the rotatable base304. In one example, fasteners308, such as thumbscrews or the like, extend through the saddle slide306and the rotatable base304. The fasteners308are disposed within slots310in the saddle slide306. In an example, the saddle slide306is slidable over the rotatable base304when the fasteners308are loosened. The saddle slide306includes an instrument guide lumen carrying the instrument guide301.

As described above, the lower portion110of the guide coupler104includes the recess118. In an example, thumbscrew312extends through the wall of saddle slide306that defines the instrument guide lumen. When tightened, the thumbscrew312engages against the surface defining the recess118to securely retain the instrument guide100within the instrument guide lumen. Thus, the recess118assists in preventing the instrument guide from moving into or out of the instrument guide lumen when the thumbscrew312is secured. In another example, the guide coupler104includes keys extending from the lower portion110. These keys are sized and shaped to fit within corresponding grooves in the trajectory alignment assembly. The relation of the keys to the grooves of the trajectory alignment assembly300substantially prevents unwanted relative rotation between the instrument guide100and the trajectory alignment system300.

In another example, the trajectory alignment assembly300is then rotationally and arcuately moveable to orient the channels206A-E of instrument guide100along a desired track through the burr hole and into the skull. In other words, the trajectories defined by channels206A-E are positionable arcuately and rotationally to extend through the burr hole and into the skull. One example of the trajectory alignment assembly300is further described in U.S. patent application Ser. No. 10/671,913, filed on Sep. 25, 2003, which is assigned to the assignee of the present application and which is incorporated by reference herein in its entirety. Additional examples of trajectory guide assemblies are shown in U.S. patent application Ser. No. 09/828,451, filed on Apr. 6, 2001, which is assigned to the assignee of the present patent application, and which is incorporated by reference herein in its entirety.

FIG. 4is a perspective view of the instrument guide100coupled to the trajectory alignment assembly300. The instrument guide100ofFIGS. 1 and 4is similar to the instrument guide301, described above. However, the instrument guide100includes an instrument passage204with an offset channel206E that is substantially parallel to a longitudinal axis of the instrument guide100, but offset therefrom.

FIG. 5is a perspective view of an instrument guide400coupled to a trajectory alignment assembly300and a translating stage500, which is also sometimes referred to as a microdrive introducer. The translating stage500includes a base502. In an example, the base502includes an orifice503within which the upper portion110of the instrument guide400is located. The upper portion110includes the recess116. A thumbscrew504, or other fastener, is tightened and engages the surface defining the recess116to retain the translating stage500around the instrument guide400. In an example, the instrument guide400is adapted to couple with the translating stage500. In one example, a first stage506is moveably coupled to the base502. In another example, the first stage506is translatable toward or away from the instrument guide400. The first stage506moves in directions substantially parallel to the channels206A-E in instrument guide400. A second stage508is moveably coupled to the first stage506. In an example, the second stage508is independently translatable toward or away from the instrument guide400.

In the example ofFIG. 5, the first stage506includes a stop510for a guide tube512. In another example, the guide tube512includes a flange that engages the stop510. The guide tube512is plunged through one of the channels206A-E of the instrument guide400. In an example, the instrument guide channels206A-E are sized and shaped to snugly pass the outer perimeter of the guide tube512. This provides an accurate track to a desired target for the guide tube512. In another example, a different instrument514is retained in a retaining assembly516coupled to the second stage508. In one example, tightening of the thumbscrew518retains the instrument514. In another example, the instrument514is plunged through the guide tube512toward a target. The guide tube512is sized and shaped to snugly pass the outer perimeter of the instrument514. The coupling of the guide layer102to the guide tube512and the coupling of the guide tube512to the instrument514provides an accurate track to the target. The trajectory defined by the substantially untapered channel206E, in this example, is translated to the instrument514and guide tube512to provide precise tracking to a desired target. The substantially untapered inner surface of the channels206A-E provides snug coupling between the guide layer102and the guide tube512so the guide tube512and instrument514mirror the trajectory of the channels206A-E.

In another example, additional tubes are disposed between the inner surface of the guide tube512and the instrument514. In one example, the instrument514has a smaller diameter, and a spacer tube is provided to snugly couple between the instrument514and the guide tube512. In still another example, the instrument514is a stimulation or sensing electrode, catheter, or the like. Additional examples of translatable stages, guide tubes, and instruments are shown in U.S. application Ser. No. 11/005,607 filed on Dec. 4, 2004, which is assigned to the assignee of the present patent application, and which is incorporated by reference herein in its entirety.

FIG. 6is a block diagram showing a method of manufacture600. As shown in block602, at least a mold having at least one pin is provided. In an example, the pin has a substantially untapered outer perimeter sized and shaped to correspond to the inner surface of the guide layer102that defines the substantially untapered instrument passage204and channels206A-E. As shown in block604, the pin is then surrounded with a hardenable material, such as Grilamid®, polycarbonate, injection molded plastics, epoxies or the like. This material hardens (i.e., solidifies) to form the first guide layer102. Then, in block606, the mold is broken away or otherwise removed from around the first guide layer102. The first guide layer102is molded in substantially the same shape as the inner surface of the mold. In one example, the inner surface of the mold substantially corresponds to the outer perimeter of the guide layer102. In one example, the inner surface of the mold includes at least one ridge disposed thereon. In another example, four ridges are positioned about 90 degrees around the mold inner surface. The ridges define corresponding grooves202on the outer perimeter of the first guide layer102. As shown in block608, the pin is removed from the first guide layer102. In one example, the first guide layer102is pushed off of the pin. In an example, the inner surface of the first guide layer102corresponds to the outer surface of the pin. In other words, the first guide layer102includes an instrument passage204and corresponding channels206A-E defined by the geometry of the pin. Because the pin has a substantially untapered outer perimeter, the instrument passage204and channels206A-E correspondingly are substantially untapered. In another example, the substantially untapered passage204and channels206A-E are formed by laser drilling, EDM and the like.

As shown in block610, the first instrument passage is aligned with a second instrument passage of the first guide layer and second guide layer, respectively. In one example, the first and second instrument passages are sized and shaped to snugly pass a medical instrument. In another example, the first guide layer102is positioned within a guide coupler, for example guide coupler104. Optionally, the first guide layer102is disposed within the guide layer lumen108, and the guide layer102is sized and shaped to snugly fit within the guide coupler104. In one example, the first guide layer102, including at least one groove202, is positioned within the guide coupler104so at least one ridge107is disposed within the groove202. In still another example, a second guide layer102is then positioned within the guide coupler104. Optionally, the second guide layer102includes a substantially untapered instrument passage204and associated channels206A-E. The channels206A-E of the second guide layer102are aligned with those of the first guide layer102. In one option, the second guide layer102includes a groove202, such that the ridge107is disposed within the groove202of the second guide layer102. This aligns the instrument passage204and channels206A-E of the first and second guide layers102.

In still another example, the first guide layer102is adhered to the second guide layer102and/or the guide coupler104. The guide layers102are affixed with adhesives, ultrasonic bonding, snaps, press pins, screws and the like. The top guide layer102and bottom guide layer102are adhered to the guide coupler104, for instance, with an adhesive including cyanoacrylate. In yet another example, the guide layers102are interference fit with the guide coupler104. Optionally, additional guide layers102are disposed within the guide coupler104to define extended passages through aligned channels206A-E. With additional guide layers102, the top guide layer102and the bottom guide layer102retain the additional guide layers102within the guide coupler104.

The various embodiments of the instrument guide and method for making the same in this document are presented as illustrative examples, and are not intended to be limiting. The instrument guide embodiments discussed in this document will be capable of use with a variety of instruments including sensing and stimulation electrodes, catheters, biopsy probes or the like. The instrument guide includes substantially untapered channels that allow snug coupling between the channels and instruments. In another example, the untapered channels allow snug coupling between the channels and tubes interposed between the channels and the instruments. In still another example, the substantially untapered channels provide snug slidable coupling between long, thin instruments and tubes.

Moreover, providing multiple aligned guide layers defines substantially untapered elongated passages that accurately track instruments fed therethrough. The tight tolerance between the inner diameter of the guide layers and the outer diameter of the instrument enhances the accuracy of guidance for the instrument while still allowing slidable movement. Accurate placement of the instrument is achieved where the instrument is aligned to a desired trajectory and maintained on the desired trajectory during plunging. Because the substantially untapered passage provides an elongated passage with a tight tolerance to the instrument, the instrument is precisely plunged into the brain, for instance, even after the instrument exits the elongated passage. As a result, a plunged instrument fed through the substantially untapered passage of the instrument guide remains parallel and coincident to a desired trajectory.

Making an instrument guide with an elongate passage without stacking guide layers requires, in one example, tapering of the channel with a correspondingly tapered molding pin. When the channel is not tapered removal of the pin often distorts the channel because the pin is drawn over a relatively long distance. Tapering of the channel helps avoid distortion as the tapered pin is drawn along the channel a shorter distance. However, the resulting tapered channel less accurately tracks instruments disposed therein because its proximal portion is less snugly fit to the instrument. As a result of the excessive clearance between the instrument and the proximal portion of the instrument guide the instrument tracks less accurately. Additionally, where it is desirable to have closely packed elongate passages, for instance in image guided surgery, using tapered channels undesirably spaces the channels from each other.

Alternatively, molding is performed around adjacent guide tube liners. As described above, in an example where the instrument guide is used in image guided surgery it is desirable to have closely packed elongate passages. Using tube liners undesirably spaces the passages from each other. Moreover, elongate passages are also drilled. However, when multiple closely spaced elongate passages are desired a drill bit can move or ‘wander,’ and break into the nearby passages.

In the method disclosed herein, when drawing the untapered pin through a guide layer the drawn distance is relatively short allowing for a substantially untapered lumen and corresponding channels. In one example, this distance is the thickness of the first layer, which is less than about a quarter of an inch. The instrument guide thus provides elongate substantially untapered passages defined by the channels of stacked guide layers.

In another example, an instrument guide having passages angled with respect to a longitudinal center axis of the instrument guide is made using the techniques described herein. In one example, separate molds are provided for each guide layer of the angled instrument guide. The separate molds include angled pins disposed within the molds. In another example, the pins are integral to the molds. The pins are selectively oriented within each mold so guide layers formed from the molds provide continuous substantially untapered and angled passages when the channels of each guide layer are aligned. In other words, the pin position within each mold is varied so that when the guide layers are stacked an angled continuous substantially untapered passage is formed. One example of an instrument guide having angled passages is further described in U.S. patent application Ser. No. 10/370,090, filed on Feb. 20, 2003, which is assigned to the assignee of the present application and which is incorporated by reference herein in its entirety.

It is to be understood that the above description is intended to be illustrative, and not restrictive. Many other embodiments will be apparent to those of skill in the art upon reading and understanding the above description. It should be noted that embodiments discussed in different portions of the description or referred to in different drawings can be combined to form additional embodiments of the present application. The scope of the invention should, therefore, be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled.