Patent Description:
When a substrate is not consistently secured in a repeatable, predictable manner regardless of substrate inconsistencies or deformities, the images may vary from substrate to substrate and it may be difficult to determine proper surface locations. As a result, practitioners, researchers, and those imaging samples on substrates continue to seek an apparatus for consistently, repeatably, and predictably securing substrates of varying inconsistencies or deformities.

<CIT> discloses an adjustable fixture for holding a sample for inspection with a scanning acoustic microscope. The fixture includes a first horizontal bar disposed on a first end of a frame, and a second horizontal bar disposed on a second end of the frame. The second horizontal bar is engaged with the frame to be movable between the first end and the second end of the frame. The adjustable fixture further includes a side bar disposed on one or more of the first side and the second side of the frame, with an end of the second horizontal bar slidable and lockable along the side bar, and an engagement mechanism releasably coupling the end of the second horizontal bar to the side bar.

<CIT> discloses a device for in situ temperature-induced antigen retrieval of samples where all steps are performed under a pressure higher than the atmospheric pressure on a sample immobilized on a sample support which can be further subjected to staining and imaging on the same sample support.

<CIT> discloses specimen carriers for holding specimens and reagents for an apparatus for performing automated sample preparation, DNA amplification and detection.

Further aspects and preferred embodiments of the invention are defined in the dependent claims. Any aspects, embodiments and examples of the present disclosure which do not fall under the scope of the appended claims are provided for illustrative purposes.

This disclosure is directed to an apparatus for securely holding a substrate, such as a microscope slide. Suitable devices, systems, and/or methods for holding a substrate may include those described in one or more of the following <CIT>; <CIT>;<CIT>; <CIT>; <CIT>; <CIT>; <CIT>.

<FIG> show a securing block <NUM>. The securing block <NUM> includes a main body <NUM> with a stopper <NUM> and a ramp <NUM>, both of which extend from the same side of the main body <NUM>. The securing block <NUM> can be configured and/or oriented to cause a substrate to travel vertically, downwardly, horizontally, orthogonally, or combinations thereof. Therefore, the securing block <NUM> can be inverted, rotated, or adjusted in any desired manner to cause the substrate to travel in at least one desired direction. In one embodiment, the securing block <NUM> provides a controlled references surface for a substrate during imaging, processing, holding, or the like. In one embodiment, the securing block <NUM> provides a flat substrate surface during imaging, processing, holding, or the like when a substrate has a non-flat (e.g., curved, twisted, warped, or the like) surface.

In one embodiment, the main body <NUM> can be a single piece. In one embodiment, the main body <NUM> can be multiple pieces, including at least two pieces. When the main body <NUM> is at least two pieces, a first piece includes the stopper <NUM> and a second piece includes the ramp <NUM>.

In one embodiment, the main body <NUM> includes at least one hole (not shown) to accept at least one fastener <NUM> for attachment to a frame or a secure bar. In one embodiment, the securing block <NUM> includes at least one height adjuster (not shown), such as a shim, to adjust the height of the securing block <NUM> relative to the frame or the secure bar.

In one embodiment, the stopper <NUM> can be any appropriate shape, including, but not limited to, triangular, hemispherical, parabolic, trapezoidal, rectangular, cubical, or the like. In one embodiment, the ramp <NUM> can be any appropriate shape, including, but not limited to, triangular, hemispherical, parabolic, trapezoidal, or the like.

<FIG> show a secure bar <NUM>. The secure bar <NUM> includes a bracket <NUM> and a strut <NUM>. The strut <NUM> includes a proximal end including a first securing block <NUM> and a distal end <NUM> including a second securing block <NUM>. In one embodiment, the bracket <NUM> and the strut <NUM> are a single piece. In one embodiment, the bracket <NUM> and the strut <NUM> are separate pieces. When the bracket <NUM> and the strut <NUM> are separate pieces, the bracket <NUM> and the strut <NUM> can be attached, adjoined, or adhered to each other by screws, dowels, rods, rivets, at least one dovetail joint, at least one tongue-and-groove joint, an adhesive, an epoxy, at least one magnet, or by any other appropriate manner in which to attach, adjoin, or adhere two or more pieces.

In one embodiment, the bracket <NUM> can include at least one bearing <NUM> to permit rotation of the bracket <NUM> relative to a substrate (not shown) or at least one other component, including, without limitation, the strut <NUM> or a frame (not shown). In one embodiment, the bracket <NUM> can include two or more bearings <NUM>.

In one embodiment, the bracket <NUM> includes a projection <NUM> extending outwardly from the bracket <NUM>. In one embodiment, the bracket <NUM> includes two projections <NUM> extending outwardly, in the same direction, from the bracket <NUM>. In one embodiment, the bracket <NUM> includes a flange <NUM> extending outwardly from the bracket <NUM> in the same direction as the projection <NUM>.

In one embodiment, the secure bar <NUM> can include at least one flexure <NUM>, such as one or more flexible materials, a cut-out (e.g., a track, a groove, a notch, or the like), a material less stiff than the other material composing the strut <NUM>, or the like. The at least one flexure <NUM> allows for movement of the securing block <NUM> via the proximal end or the distal end <NUM> of the secure bar <NUM> to move along a given axis (for example, the z-axis) relative to the other end of the secure bar <NUM>. The at least one flexure <NUM> can extend at least partially through a top face of the strut <NUM>, can extend at least partially through a bottom face of the strut <NUM>, can extend at least partially through a side face of the strut <NUM>, or can extend entirely across the strut <NUM>. The segment including the at least one flexure <NUM> can also include a clasp <NUM> to set the position, angle, location, or the like along the given axis (for example, the z-axis) of the segment incuding the securing block <NUM> and the at least one flexure <NUM> once the desired position, angle, location, or the like has been determined. The clasp <NUM> can include, but is not limited to, screws, dowels, rods, and rivets. The clasp <NUM> can also be used to adjust position, angle, location, or the like of the segment including the at least one flexure <NUM>. In one embodiment, the distal end <NUM> of the strut <NUM> can be adjusted (i.e., angle, position, location, or the like), such as by translating, flexing, bending, twisting, or moving, relative to, and/or independently of, the proximal end of the strut <NUM>. The distal end <NUM> can also include at least one securing block <NUM>. In one embodiment, the proximal end of the strut <NUM> can be adjusted (i.e., angle, position, location, or the like), such as by translating, flexing, bending, twisting, or moving, relative to, and/or independently of, the distal end <NUM> of the strut <NUM>. The proximal end can also include at least one securing block <NUM>.

<FIG> show a secure bar <NUM>. The secure bar <NUM> is similar to the secure bar <NUM>, except that secure bar <NUM> includes a projection <NUM> at a distal end of a bracket <NUM>. The secure bar <NUM> includes the bracket <NUM> and a strut <NUM>. The strut <NUM> includes a proximal end including a first securing block <NUM> and a distal end <NUM> including a second securing block <NUM>. In one embodiment, the bracket <NUM> and the strut <NUM> are a single piece. In one embodiment, the bracket <NUM> and the strut <NUM> are separate pieces. When the bracket <NUM> and the strut <NUM> are separate pieces, the bracket <NUM> and the strut <NUM> can be attached, adjoined, or adhered to each other by screws, dowels, rods, at least one dovetail joint, at least one tongue-and-groove joint, an adhesive, an epoxy, at least one magnet, or by any other appropriate manner in which to attach, adjoin, or adhere two or more pieces.

In one embodiment, the bracket <NUM> can include at least one bearing <NUM> to permit rotation of the bracket <NUM> relative to a substrate (not shown) or at least one other component, including, without limitation, the strut <NUM> or a frame (not shown).

In one embodiment, the bracket <NUM> includes a projection <NUM> extending outwardly from the bracket <NUM>. In one embodiment, the bracket <NUM> includes two projections <NUM> extending outwardly, in the same direction, from the bracket <NUM>.

In one embodiment, the secure bar <NUM> can include at least one flexure <NUM>, such as one or more flexible materials, a cut-out (e.g., a track, a groove, a notch, or the like), a material less stiff than the other material composing the strut <NUM>, or the like. The at least one flexure <NUM> allows for movement of the securing block <NUM> via the proximal end or the distal end <NUM> of the secure bar <NUM> to move along a given axis (for example, the z-axis) relative to the other end of the secure bar <NUM>. The at least one flexure <NUM> can extend at least partially through a top face of the strut <NUM>, can extend at least partially through a bottom face of the strut <NUM>, can extend at least partially through a side face of the strut <NUM>, or can extend entirely across the strut <NUM>. The segment including the at least one flexure <NUM> can also include a clasp to set the position, angle, location, or the like along the given axis (for example, the z-axis) of the segment incuding the securing block <NUM> and the at least one flexure <NUM> once the desired position, angle, location, or the like has been determined. The clasp can include, but is not limited to, screws, dowels, rods, and rivets. The clasp can also be used to adjust position, angle, location, or the like of the segment including the at least one flexure <NUM>. In one embodiment, the distal end <NUM> of the strut <NUM> can be adjusted (i.e., angle, position, location, or the like), such as by translating, flexing, bending, twisting, or moving, relative to, and/or independently of, the proximal end of the strut <NUM>. The distal end <NUM> can also include at least one securing block <NUM>. In one embodiment, the proximal end of the strut <NUM> can be adjusted (i.e., angle, position, location, or the like), such as by translating, flexing, bending, twisting, or moving, relative to, and/or independently of, the distal end <NUM> of the strut <NUM>. The proximal end can also include at least one securing block <NUM>.

<FIG> show a holder <NUM>. The holder <NUM> includes a frame <NUM> and the secure bar <NUM>. The frame <NUM> includes a first arm <NUM> and a second arm <NUM>. The secure bar <NUM> can move, rotate, or translate freely and independently of the frame <NUM>, such as having an open position (i.e., to permit the insertion of a substrate) and a closed position (i.e., to permit the secure holding of the substrate). The holder <NUM> includes a cavity <NUM> which is formed by the secure bar <NUM> and the frame <NUM>, and which is sized and shaped to fit and accept a substrate (not shown). The first and second arms <NUM>, <NUM> are joined at proximal ends. In one embodiment, the first arm <NUM> is longer than the second arm <NUM>. In one embodiment, the second arm <NUM> is longer than the first arm <NUM>. In one embodiment, the first and second arms <NUM>, <NUM> are equal in length. In one embodiment, the frame <NUM> is a single piece. In one embodiment, the frame <NUM> is at least two pieces, such that the first arm <NUM> is part of or fully forms a first piece and the second arm <NUM> is part of or fully forms a second piece.

It should be noted that the movement, rotation, or translation of the secure bar <NUM>, <NUM> from the open position to closed position (and vice versa) causes the entirety of the secure bar <NUM>, <NUM> to move, rotate, or translate. However, the movement, rotation, or translation of the secure bar <NUM>, <NUM> is different than the movement or adjustment of the at least one securing block via the proximal or distal ends along a given axis. Therefore, adjustment of at least one securing block <NUM> along a given axis is such that at least one securing block <NUM> can be adjusted (i.e., angle, position, location, or the like) by translating, flexing, bending, twisting, or moving the segment of the secure bar <NUM>, <NUM> or the frame <NUM>, <NUM> on which the at least one securing block <NUM> is located relative to, and/or independently of, other segments of the secure bar <NUM>, <NUM> or the frame <NUM>, <NUM>. In other words, for example, the entirety of the secure bar <NUM>, <NUM> can have a first motion for opening and closing, and then a segment of the secure bar <NUM>, <NUM> can have a second motion for adjusting the at least one securing block <NUM> located on or at that segment.

The secure bar <NUM> is proximal to the distal end of the first arm <NUM>. In one embodiment, the first arm <NUM> is connected to the strut <NUM> of the secure bar <NUM>. In one embodiment, the first arm <NUM> is connected to the bracket <NUM> of the secure bar <NUM>. In one embodiment, the first arm <NUM> is connected to at least one bearing <NUM> of the secure bar <NUM>.

In one embodiment, an inner surface of the first arm <NUM> includes a platform <NUM> at least partially located between the proximal and distal ends. The platform <NUM> can support the substrate (not shown).

The second arm <NUM> includes at least two securing blocks <NUM>. In one embodiment, each of the securing blocks <NUM> of the second arm <NUM> are directly across the cavity <NUM> from the corresponding securing blocks <NUM> of the secure arm <NUM>. In one embodiment, at least one of the securing blocks <NUM> is not directly across the cavity <NUM> from the corresponding securing block <NUM> of the secure bar <NUM>. In one embodiment, the distal end of second arm <NUM> includes a pedestal <NUM> extending towards the secure bar <NUM>. The pedestal <NUM> can support the substrate (not shown).

The secure bar <NUM> has an open position and a closed position. In one embodiment, the secure bar <NUM> of the holder <NUM> is moved from the open position to the closed postion, and vice versa, by a motor (not shown, see <FIG>). The motor (not shown) is adjoined to or connected to the at least one projection <NUM> and/or the flange <NUM>. In one embodiment, the motor (not shown) is adjoined to or connected to the at least one projection <NUM> and/or the flange <NUM> by a coupling (not shown). In one embodiment, the motor (not shown) is directly adjoined to or connected to the at least one projection <NUM> and/or the flange <NUM>.

In one embodiment, at least one securing block <NUM> is adjustable along a given axis (for example, the z-axis), while the other securing blocks <NUM> are stationary, excluding adjusting the height relative to the frame <NUM> or the secure bar <NUM>. In one embodiment, all of the securing blocks <NUM> are adjustable along a given axis (for example, the z-axis).

In one embodiment, at least one of the first or second arms <NUM>, <NUM> of the frame <NUM> includes at least one flexure (not shown), such as one or more flexible materials, a cut-out (e.g., a track, a groove, a notch, or the like), a material less stiff than the other material composing the frame, or the like. For example, the second arm can include the at least one flexure (not shown) to allow for movement of the securing block <NUM> via the proximal end or the distal end of the second arm <NUM> (depending on the location of the at least one flexure within the second arm <NUM>, for example) to move along a given axis (for example, the z-axis) relative to the other end of the second arm <NUM>. The at least one flexure (not shown) can extend at least partially through a top face of the second arm <NUM>, can extend at least partially through a bottom face of the second arm <NUM>, can extend at least partially through a side face of the second arm <NUM>, or can extend entirely across the second arm <NUM>. The segment including the at least one flexure (not shown) can also include a clasp (not shown) to set the position, angle, location, or the like along the given axis (for example, the z-axis) of the segment incuding the securing block <NUM> and the at least one flexure (not shown) once the desired position, angle, location, or the like has been determined. The clasp (not shown) can include, but is not limited to, screws, dowels, rods, and rivets. The clasp (not shown) can also be used to adjust position, angle, location, or the like of the segment including the at least one flexure (not shown). In one embodiment, the distal end of the second arm <NUM> can be adjusted (i.e., angle, position, location, or the like), such as by translating, flexing, bending, twisting, or moving, relative to, and/or independently of, the proximal end of the second arm <NUM>. The distal end can also include at least one securing block <NUM>. In one embodiment, the proximal end of the second arm <NUM> can be adjusted (i.e., angle, position, location, or the like), such as by translating, flexing, bending, twisting, or moving, relative to, and/or independently of, the distal end of the second arm <NUM>. The proximal end can also include at least one securing block <NUM>.

In one embodiment, all of the securing blocks <NUM> have the same configuration and design. In one embodiment, at least one of the securing blocks <NUM> has a configuration and/or design different than the other securing blocks <NUM>.

<FIG> show a holder <NUM>. The holder <NUM> is similar to the holder <NUM>, except that the holder <NUM> includes the secure bar <NUM>. The holder <NUM> includes a frame <NUM> and the secure bar <NUM>. The frame <NUM> includes a first arm <NUM> and a second arm <NUM>. The secure bar <NUM> can move, rotate, or translate freely and independently of the frame <NUM>. The holder <NUM> includes a cavity <NUM> which is formed by the secure bar <NUM> and the frame <NUM>, and which is sized and shaped to fit and accept a substrate (not shown). The first and second arms <NUM>, <NUM> are joined at proximal ends. In one embodiment, the first arm <NUM> is longer than the second arm <NUM>. In one embodiment, the second arm <NUM> is longer than the first arm <NUM>. In one embodiment, the first and second arms <NUM>, <NUM> are equal in length. In one embodiment, the frame <NUM> is a single piece. In one embodiment, the frame <NUM> is at least two pieces, such that the first arm <NUM> is part of or fully forms a first piece and the second arm <NUM> is part of or fully forms a second piece.

The second arm <NUM> includes at least two securing blocks <NUM>. In one embodiment, each of the securing blocks <NUM> of the second arm <NUM> are directly across the cavity <NUM> from the corresponding securing blocks <NUM> of the secure bar <NUM>. In one embodiment, at least one of the securing blocks <NUM> is not directly across the cavity <NUM> from the corresponding securing block <NUM> of the secure bar <NUM>. In one embodiment, the distal end of second arm <NUM> includes a pedestal <NUM> extending towards the secure bar <NUM>. The pedestal <NUM> can support the substrate (not shown).

The secure bar <NUM> can also include a spring <NUM> to pre-load the secure bar <NUM> and/or at least one bearing <NUM> of the secure bar <NUM>. In one embodiment, the spring <NUM> is connected to the first arm <NUM>. In one embodiment, the spring <NUM> is connected to another element, such as a mount (not shown, see <FIG>). In one embodiment, the spring <NUM> is connected to the first arm <NUM> and the mount (not shown, see <FIG>).

In one embodiment, though the distal end <NUM> is adjustable, the other securing blocks <NUM> are stationary, excluding adjusting the height relative to the frame <NUM> or the secure bar <NUM>.

<FIG> show a holder <NUM>. In one embodiment, as shown in <FIG>, the holder <NUM> includes two holders <NUM>, <NUM>. In one embodiment, the holder <NUM> includes two holders, both of which are the holder <NUM>. In one embodiment, the holder <NUM> includes two holders, both of which are the holder <NUM>.

The holder <NUM> includes a motor <NUM> and a coupling <NUM>. Though the motor <NUM> and the coupling <NUM> are shown in <FIG> for the holder <NUM>, the motor <NUM> and the coupling <NUM> can be used in any embodiment of any holder discussed herein or any equivalent thereof.

In one embodiment, the holder <NUM> includes a slider <NUM> and a connector <NUM>. The slider <NUM> is adjoined or connected to the secure bar <NUM>. The connector <NUM> can be adjoined to a mount (not shown). A portion of the slider <NUM> can be fit within a track or groove of the connector <NUM>, thereby permitting movement of the slider <NUM> along a single or given plane, such that the secure bar <NUM> can translate between the open and closed positions via the motor <NUM> and the coupling <NUM>. Though the slider <NUM> and the connector <NUM> are shown in <FIG> for the holder <NUM>, the slider <NUM> and the connector <NUM> can be used in any embodiment of any holder discussed herein or any equivalent thereof.

In one embodiment, a leaf spring (not shown) can be used in place of both the slider <NUM> and the connector <NUM>.

In one embodiment, the holder <NUM> can be attached to a secondary device, such as a scanner or an imaging microscope or a fluorescence microscope, for imaging and/or processing by a mount <NUM> (i.e. a screw, a nail, a peg, a pin, a nut and bolt, a dowel, a staple, a rivet, or the like), by an adhesive, by welding, by clips, by detents, by tongue and groove joint, or the like. The holder <NUM> and/or the mount <NUM> can include at least one hole to accommodate an attachment mechanism for proper, secure attachment to the secondary device. Though the mount <NUM> is shown in <FIG> for the holder <NUM>, the mount <NUM> can be used in any embodiment of any holder discussed herein or any equivalent thereof. In one embodiment, the holder <NUM> can be attached to a secondary device for imaging and/or processing by the attachment mechanism (i.e. a screw, a nail, a peg, a pin, a nut and bolt, a dowel, a staple, a rivet, or the like), by an adhesive, by welding, by clips, by detents, by tongue and groove joint, or the like. The holder <NUM> can include at least one hole to accommodate the attachment mechanism for proper, secure attachment to the secondary device. Though the attachment mechanism is discussed for the holder <NUM>, the attachment mechanism can be used in any embodiment of any holder discussed herein or any equivalent thereof.

In one embodiment, the mount <NUM> can be adjusted, such as by the attachment mechanisms, to be planar (i.e., parallel to or coplanar with) with an imaging plane (for example, a x-y plane).

For the sake of convenience, the methods are described with reference to a slide as an example substrate and with the holder <NUM>. But the methods described below are not intended to be so limited in their scope of application. The methods, in practice, may be used with any kind of substrate (for example, without limitation, a well plate) and with any embodiment of holder, secure bar, or securing block.

In one embodiment, a reference slide is inserted into the holder <NUM>. The reference slide can be placed onto the platform <NUM> and the pedestal <NUM> or can be placed in direct contact at least two of the securing blocks <NUM>. The secure bar <NUM> is in the open position. The secure bar <NUM> is moved into the closed position. The ramps <NUM> of the respective securing blocks <NUM> lift the reference slide up and the stoppers <NUM> of the respective securing blocks <NUM> set the maximum lift distance for the reference slide and constrain the reference slide. When the secure bar <NUM> is set in the closed position, the force exerted on the reference slide by the securing blocks <NUM> inhibits translational movement of the reference slide relative to the holder <NUM>. The securing block <NUM> at the distal end <NUM> of the secure bar <NUM> can be adjusted to account for any warpage or deformations in the reference slide, thereby making the reference slide planar or substantially planar with an imaging plane (for example, the x-y plane). Once the reference slide is secured, such that the planarity of the reference slide is confirmed or observed in any appropriate manner, the secure bar is moved into the open position to release the forces on the slide. The ramps of the respective securing blocks guide the slide down. The reference slide is then removed from the holder and an experimental slide (i.e., a slide include a sample to be imaged) is inserted to restart the process.

In one embodiment, the method discussed above excludes a reference slide and is done on a slide-by-slide basis (i.e., inserted, secure bar closed, securing block adjusted, etc.). In one embodiment, the method discussed above excludes a reference slide and is done for the first experimental slide with the adjustment to the securing block <NUM> being retained for all subsequent experimental slides.

Additionally, though "first" and "second" are used, the terms are not intended to limit various features/elements to only one or two. Rather, three (i.e., third), four (i.e., fourth), or more may be included or used where appropriate or desirous to do so.

For example, a numeric value may have a value that is +/- <NUM>% of the stated value (or range of values), +/- <NUM>% of the stated value (or range of values), +/- <NUM>% of the stated value (or range of values), +/-<NUM>% of the stated value (or range of values), +/- <NUM>% of the stated value (or range of values), etc. Any numerical values given herein should also be understood to include about or approximately that value, unless the context indicates otherwise.

Claim 1:
A device, comprising:
a frame (<NUM>) comprising a first arm (<NUM>) and a second arm (<NUM>), wherein the second arm includes at least two securing blocks (<NUM>);
a secure bar (<NUM>, <NUM>) comprising at least two securing blocks (<NUM>); and
a flexure (<NUM>, <NUM>),
wherein the at least two securing blocks of the second arm and the at least two securing blocks of the secure bar are on opposing sides of a cavity (<NUM>),
wherein (i) one end of the secure bar is adjustable relative to the other end of the secure bar, or (ii) one end of the second arm is adjustable relative to the other end of the second arm,
wherein at least one of the securing blocks is at the adjustable end of the secure bar or at the adjustable end of the second arm,
wherein the adjustable end of the secure bar or the adjustable end of the second arm is adjustable along essentially a z-axis,
wherein the flexure is configured to permit adjustment of the adjustable end of the secure bar or the adjustable end of the second arm,
wherein the flexure is also configured to adjust at least one of the position, angle, or location of at least one of the at least two securing blocks of the secure bar or at least one of the at least two securing blocks of the second arm, and
wherein the flexure is configured to adjust at least one of the position, angle, or location of one of the at least two securing blocks of the secure bar independently of the other one of the at least two securing blocks of the secure bar.