Methods and devices for retaining lyophilized reagent cake in reagent wells and rehydrating and withdrawing the lyophilized reagent cake

Abstract

A reagent cartridge for a library preparation system that enhances retention of lyophilized reagent cakes. The reagent cartridge includes a cartridge body having a side wall, and an opening at a first end, the cartridge body being closed at a second end. A lyophilized reagent is disposed in the cartridge body.

Description

METHODS AND DEVICES FOR RETAINING LYOPHILIZED REAGENT CAKE IN REAGENT WELLS AND REHYDRATING AND WITHDRAWING THE LYOPHILIZED REAGENT CAKECROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 613,536 , filed December 21 , 2023, and entitled “METHODS AND DEVICES FOR RETAINING LYOPHILIZED REAGENT CAKE IN REAGENT WELLS AND REHYDRATING AND WITHDRAWING THE LYOPHILIZED REAGENT CAKE”, which is incorporated herein by reference in its entirety.

[0002] The present application generally relates to library preparation systems, and more specifically to library preparation systems including reagent cartridges or wells that enhance retainment of lyophilized reagent cake in the reagent cartridge or well and ease rehydration and extraction of the lyophilized reagent cake.BACKGROUND

[0003] Library preparation systems generally include working areas where an assay is stored, consumable areas for storing additives, such as reagents and other consumables used for library preparation, and loading areas, for loading and / or transferring a prepared sample to a system such as a sequencing system. Each of these areas generally includes an array of wells, containers, or cartridges that hold the various components (e.g., samples, reagents, disposable tips, etc.). In some cases, reagent may be pre-loaded individual reagent cartridges and the reagent may be lyophilized prior for storage and / or shipping where the lyophilized reagent is rehydrated and extracted by the library preparation system before use.SUMMARY

[0004] Shortcomings of the prior art can be overcome, and benefits as described in this disclosure can be achieved, through systems and devices for increasing the density of container or cartridge arrays, which reduces the area footprint of such cartridge arrays, in a library preparation system. Various implementations of the systems and devices are described below, and the systems and devices in any combination, may overcome these shortcomings and achieve the benefits described herein.

[0005] In a first implementation, a reagent cartridge for a library preparation system includes a cartridge body having a side wall, and an opening at a first end, the cartridgebody being closed at a second end. The cartridge body has a high height to width aspect ratio. A lyophilized reagent is disposed in the cartridge body.

[0006] In a second implementation, a reagent cartridge for a library preparation system includes a cartridge body having a side wall, and an opening at a first end, the cartridge body being closed at a second end. The cartridge body has a non-cylindrical shape. A lyophilized reagent is disposed in the cartridge body.

[0007] In a third implementation, a reagent cartridge for a library preparation system includes a cartridge body having a side wall, and an opening at a first end, the cartridge body being closed at a second end. The cartridge body has an internal roughened surface. A lyophilized reagent is disposed in the cartridge body.

[0008] In a fourth implementation, a reagent cartridge for a library preparation system includes a cartridge body having a side wall, and an opening at a first end, the cartridge body being closed at a second end and the cartridge body having an internal projection. A lyophilized reagent is disposed in the cartridge body.

[0009] In a fifth implementation, a reagent cartridge for a library preparation system includes a cartridge body having a side wall, and an opening at a first end, the cartridge body being closed at a second end and the cartridge body side wall comprising a hydrophobic coating. A lyophilized reagent is disposed in the cartridge body.

[0010] In a sixth implementation, a reagent cartridge for a library preparation system includes a cartridge body having a side wall, and an opening at a first end, the cartridge body being closed at a second end. An enriched lyophilized reagent is disposed in the cartridge body.

[0011] In a seventh implementation, a reagent cartridge for a library preparation system includes a cartridge body having a side wall, and an opening at a first end, the cartridge body being closed at a second end. The cartridge body comprises a hydrophilic coating in a hydrophilic region and a hydrophobic coating in a hydrophobic region on an inner surface of the cartridge body side wall. A lyophilized reagent is disposed in the cartridge body.

[0012] In an eighth implementation, a reagent cartridge for a library preparation system includes a cartridge body having a side wall, and an opening at a first end, the cartridge body being closed at a second end. The cartridge body has a non-circular cross- sectional shape. A lyophilized reagent is disposed in the cartridge body.

[0013] In a ninth implementation, a reagent cartridge for a library preparation system includes a cartridge body having a side wall, and an opening at a first end, the cartridgebody being closed at a second end. The cartridge body is sized and shaped to cooperate with an aspirator tip so that the aspirator tip fills more than 90% of the volume of the cartridge body when the aspirator tip is fully inserted into the cartridge body. A liquid reagent is disposed in the cartridge body.

[0014] In a tenth implementation, a reagent cartridge for a library preparation system includes a cartridge body having a side wall, and an opening at a first end, the cartridge body being closed at a second end. The cartridge body includes a deformable portion proximate the closed second end. A liquid reagent is disposed in the cartridge body.

[0015] In further accordance with the foregoing the first through tenth implementations, the reagent cartridge may further include or comprise any one or more of the following features.

[0016] In an implementation, the height to width aspect ratio is greater than 3:1 .

[0017] In another implementation, the height to width aspect ratio is greater than 5:1 .

[0018] In yet another implementation, at least part of the cartridge body is substantially cylindrical.

[0019] In yet another implementation, at least part of the cartridge body is substantially conical.

[0020] In yet another implementation, the conical part of the cartridge body narrows from top to bottom.

[0021] In yet another implementation, the cartridge body narrows from bottom to top.

[0022] In yet another implementation, the cartridge body includes two substantially conical parts that join together to form a substantially hour-glass shape.

[0023] In yet another implementation, at least part of the cartridge body is substantially cylindrical.

[0024] In yet another implementation, the roughened surface is part of the cartridge body side wall.

[0025] In yet another implementation, the roughened surface is formed by a coating on the cartridge body side wall.

[0026] In yet another implementation, the internal projection is a single ledge extending inward from an inner surface of the cartridge body side wall.

[0027] In yet another implementation, the internal projection is annular in shape.

[0028] In yet another implementation, the cartridge body side wall includes a plurality of internal projections.

[0029] In yet another implementation, the plurality of internal projections extend in a height direction along the cartridge body side wall.

[0030] In yet another implementation, the hydrophilic coating is 4 pm or less.

[0031] In yet another implementation, the hydrophilic coating is 2 pm or less.

[0032] In yet another implementation, the hydrophilic coating comprises polydimethylsiloxane.

[0033] In yet another implementation, the enriched lyophilized reagent comprises a reagent and an enriching agent.

[0034] In yet another implementation, the enriching agent comprises polyethylene glycol (PEG).

[0035] In yet another implementation, the hydrophobic coating is disposed at least partially between the opening and the hydrophilic coating.

[0036] In yet another implementation, a hydrophilic guide extends from the hydrophilic region to the opening.

[0037] In yet another implementation, the hydrophilic coating comprises a lubricant.

[0038] In yet another implementation, the lubricant comprises oil.

[0039] In yet another implementation, the non-circular cross-sectional shape is a substantially square-shape.

[0040] In yet another implementation, the non-circular cross-sectional shape is a substantially diamond-shape.

[0041] In yet another implementation, the non-circular cross-sectional shape is a substantially oval-shape.

[0042] In yet another implementation, the substantially oval-shape includes a secondary smaller oval-shaped lobe.

[0043] In yet another implementation, the aspirator tip causes the reagent within the cartridge body to rise more than 50% higher than a level of reagent in the cartridge body without the aspirator tip fully inserted.

[0044] In yet another implementation, the shape of an outer surface of the aspirator tip is complementary to the shape of an inner surface of the reagent cartridge body.

[0045] In yet another implementation, the deformable portion deforms inwardly to reduce the interior volume of the cartridge body proximate the deformable portion.

[0046] In yet another implementation, a surface level of the liquid reagent rises within the interior volume when the deformable portion deforms inwardly.BRIEF DESCRIPTION OF THE DRAWINGS

[0047] FIG. 1 is a top view of a library preparation system.

[0048] FIG. 2 is a front view of the system of FIG. 1 .

[0049] FIG. 3 is an isometric view of the system of FIG. 1 .

[0050] FIG. 4A includes side views of first examples of reagent cartridges constructed in accordance with the teachings of the disclosure, the shape of the reagent cartridges enhancing retention of lyophilized reagent;

[0051] FIG. 4B is a side view of a second example of a reagent cartridge constructed in accordance with the teachings of the disclosure, the shape of the reagent cartridge enhancing retention of lyophilized reagent;

[0052] FIG. 5 includes side views of third examples of reagent cartridges constructed in accordance with the teachings of the disclosure, the interior wall roughness enhancing retention of lyophilized reagent;

[0053] FIG. 6A includes side views of fourth examples of reagent cartridges constructed in accordance with the disclosure, the interior of the cartridge having ledges enhancing retention of lyophilized reagent;

[0054] FIG. 6B is a side view of a fifth example of a reagent cartridge constructed in accordance with the disclosure, the interior of the cartridge having alternate ledges enhancing retention of lyophilized reagent;

[0055] FIG. 7A is a side view of a sixth example of a portion of a reagent cartridge body wall constructed in accordance with the disclosure, the interior of the reagent cartridge body wall including a chemical coating that enhances retention of lyophilized reagent;

[0056] FIG. 7B is a schematic illustration of a method that may be used to produce the reagent cartridge of FIG. 7A;

[0057] FIG. 8 is a schematic illustration of a process for creating an enhanced lyophilized reagent cake that chemically enhances retention within a reagent cartridge;

[0058] FIGS. 9A and 9B are side cross-sectional views of a seventh example of a reagent cartridge constructed in accordance with the teachings of the disclosure, the reagent cartridges having interior coatings that aid in rehydration of lyophilized reagent cakes.

[0059] FIG. 10 includes partial side views of a wall of a reagent cartridge body wall constructed in accordance with the teachings of the disclosure, the reagent cartridge body wall including surface features and lubricant that aids in rehydration of lyophilized reagent cakes.

[0060] FIGS. 11 A and 11 B are top and perspective views, respectively, of a plurality of reagent cartridges constructed in accordance with the teachings of the disclosure, the reagent cartridges enhancing rehydrated reagent extraction.

[0061] FIGS. 12A and 12B are side views of a plurality of reagent cartridges and a plurality of liquid aspiration tips constructed in accordance with the teachings of the disclosure, the liquid aspiration tips and the reagent cartridge cooperating to enhance rehydrated reagent extraction.

[0062] FIGS. 13A and 13B are side views of a liquid aspiration tip and a reagent cartridge constructed in accordance with the teachings of the disclosure, the reagent cartridge having a deformable tip to enhance rehydrated reagent extraction.DETAILED DESCRIPTION

[0063] Although the following text discloses a detailed description of implementations of methods, apparatuses and / or articles of manufacture, it should be understood that the legal scope of the property right is defined by the words of the claims set forth at the end of this patent. Accordingly, the following detailed description is to be construed as examples only and does not describe every possible implementation, as describing every possible implementation would be impractical, if not impossible. Numerous alternative implementations could be implemented, using either current technology or technology developed after the filing date of this patent. It is envisioned that such alternative implementations would still fall within the scope of the claims.

[0064] At least one aspect of this disclosure is related to creating reagent cartridges that reduce or prevent lyophilized reagent cakes within the reagent cartridges from becoming dislodged and changing orientation during transport or movement.

[0065] Another aspect of this disclosure is related to enhancing the rehydration process for lyophilized reagent cakes by enhancing rehydration delivery and contact with the lyophilized reagent cakes in the reagent cartridge.

[0066] Yet another aspect of this disclosure is related to enhancing extraction of liquid reagent from reagent cartridges.

[0067] A library preparation system 200 is illustrated in FIGS. 1 -3. The library preparation system 200 may include one or more consumables areas 302, a first working area 304 optionally having two working bays 304A, 304B, an optional second working area 306, and a loading area. In at least some embodiments, the first working area 304 may be referred to as an assay bay and the second working area 306 may be referred to as a common resource bay. In other implementations, the library preparation system may include a single working area 304.

[0068] The consumable areas 302 may include one or more consumable receptacles that may be used to load and store reagents and consumables needed for a library preparation process, including, disposable tips, wet or dry assay specific reagents, wet or dry bulk reagents, and reaction plates and wells. The consumables, such as reagent, may be stored in an array, for example an array 111 of individual reagent cartridges 154.Securing Lyophilized Reagent Cakes in a Reagent Cartridge

[0069] As discussed above, reagent cartridges may be pre-loaded with reagent and the reagent may be lyophilized forming a cake within the reagent cartridge prior for storage and / or shipping. The lyophilized reagent is rehydrated and extracted by the library preparation system before use. However, during transport and / or movement, for example movement during the rehydration process, the lyophilized reagent cake may become dislodged from the sides of the reagent cartridge and the lyophilized reagent cake can become unfavorably oriented within the reagent cartridge for the rehydration process. For example, the lyophilized reagent cake can become lodged near the top of the reagent cartridge. As a result, when the rehydration process introduces liquid into the reagent cartridge, the liquid does not mix with the entire lyophilized reagent cake and some of the reagent may not become completely rehydrated. In order to enhance complete rehydration and no loss of reagent material, the lyophilized reagent cake should maintain position in the bottom of the reagent cartridge.Reagent Cartridge Body size / shape

[0070] Turning now to FIG. 4A, a typical reagent cartridge 54 is illustrated on the left side. The reagent cartridge 54 includes a cartridge body 60 having a side wall 62, and an opening 64 at a first end 66, the cartridge body 60 being closed at a second end 68.

[0071] In the middle and right side of FIG. 4A, two example reagent cartridges 154 are illustrated that are constructed in accordance with the teachings of the disclosure. Thetwo reagent cartridges 154 include a cartridge body 160 having a side wall 162, and an opening 164 at a first end 166, the cartridge body 160 being closed at a second end 168, similar to the reagent cartridge 54 on the right side. However, the reagent cartridges 154 on the left side have a high height to width aspect ratio. In some examples, the high height to width aspect ratio is more than 3:1 , preferably more than 5:1 . A lyophilized reagent 170 is disposed in the cartridge body 154.

[0072] The high height to width aspect ratio exposes more of the lyophilized reagent 170 to the inner surfaces of the side wall 162, which provides a larger area to which the lyophilized reagent 170 adheres, thereby forming a more secure connection between the lyophilized reagent 170 and the side wall 162, which reduces the chances of the lyophilized reagent 170 from becoming dislodged. Furthermore, if the lyophilized reagent 170 does become dislodged from the side wall 162, there is less space within the reagent cartridge for the lyophilized reagent 170 to become mis-oriented.

[0073] In some examples, for example the middle reagent cartridge 154 in FIG. 4A, at least part of the cartridge body 160 is substantially cylindrical.

[0074] In some examples, for example the right reagent cartridge 154 in FIG. 4A, at least part of the cartridge body 160 is substantially conical. The substantially conical portion of the cartridge body 160 may narrows from top to bottom, as illustrated in FIG. 4A. In other examples, the substantially conical portion of the cartridge body 160 narrows from bottom to top.

[0075] Turning now to FIG. 4B, another reagent cartridge 154 is illustrated that includes a cartridge body 160 having a side wall 162, and an opening 164 at a first end 166, the cartridge body 160 being closed at a second end 168. The cartridge body 160 has a non-cylindrical shape. A lyophilized reagent 170 is disposed in the cartridge body. The cartridge body 160 includes a first substantially conical part 172 and a second substantially conical part 174 that join together to form a substantially hour-glass shape. The substantially hour-glass shape maintains the lyophilized reagent 170 in the bottom portion of the cartridge body 160 because even if the lyophilized reagent 170 becomes detached from the side wall 162, the lyophilized reagent 170 will not slide upwards as the container body 160 includes the narrowest portion between the substantially conical part 172 and the second substantially conical part 174.Wall roughness

[0076] Turning now to FIG. 5, other implementations of reagent cartridges 154 are illustrated. The reagent cartridges 154 include a cartridge body 160 having a side wall 162, and an opening 164 at a first end 166, the cartridge body 160 being closed at a second end168. The cartridge body 160 has an internal roughened surface176. A lyophilized reagent 170 is disposed in the cartridge body 160.

[0077] In some examples, the roughened surface 176 is part of the cartridge body side wall 162, as in the embodiment on the left side of FIG. 5. In other implementations, the roughened surface 176 is formed by a coating 178 on the cartridge body side wall 162, as illustrated on the right side of FIG. 5.

[0078] In yet other examples, the roughened surface 176, whether part of the cartridge body side wall 162 or part of a coating 178, does not affect optical properties of the cartridge body 160, which is advantageous particularly when optical properties of the reagent 170 are used.Physical stops

[0079] Turning now to FIG. 6A, other implementations of reagent cartridges 154 are illustrated. The reagent cartridges 154 include a cartridge body 160 having a side wall 162, and an opening 164 at a first end 166, the cartridge body 160 being closed at a second end 168. The cartridge body 160 includes one or more internal projections 180. A lyophilized reagent 170 is disposed in the cartridge body 160.

[0080] In some examples, the internal projection 180 is a single ledge extending inward from an inner surface of the cartridge body side wall 162, as illustrated on the left side of FIG. 6A. In other examples, the internal projection 180 is annular in shape. In yet another examples, the cartridge body side wall 162 includes a plurality of internal projections 180, as illustrated on the right side of FIG. 6A. In yet other examples, one or more of the internal projections 180 may be annularly-shaped. The internal projections 180 form physical stops that keep the lyophilized reagent 170 in its proper orientation within the cartridge body 160 even if the lyophilized reagent 170 becomes dislodged from the side wall 162.

[0081] As illustrated in FIG. 6B, in yet another implementations, the plurality of internal projections 180 may extend in a height direction along the cartridge body side wall 162. The lyophilized reagent becomes wedged between the internal projections 180 and the internal projections keep the lyophilized reagent 170 from moving within the cartridge body 162 of from becoming dislodged from the cartridge body side wall 162.Surface coatings

[0082] Turning now to FIG. 7A, in another implementation, the side wall 162 of a reagent cartridge for a library preparation system is illustrated. The reagent cartridge includes a cartridge body having the side wall 162, and an opening at a first end, thecartridge body 160 being closed at a second end, as shown in earlier implementations. The cartridge body side wall 162 comprises a hydrophobic coating 182. A lyophilized reagent is disposed in the cartridge body, but not shown in FIG. 7A. FIG. 7B illustrates a method of forming the hydrophobic coating 182. In some implementations, the hydrophilic coating 182 may be 4 pm or less. In other implementations, the hydrophilic coating 182 may be 2 pm or less. In some implementations, the hydrophilic coating 182 comprises polydimethylsiloxane.

[0083] Hydrophobic coatings on the inner surface of the cartridge body side wall 162 may be located where the lyophilized reagent would not be desirable. During loading of the reagent cartridge, the hydrophobic coating will urge the liquid reagent into a desired location, such as the bottom of the reagent cartridge body, or a location in the reagent cartridge body where the reagent will be more secure when lyophilized.Reagent and additive mixture

[0084] Turning now to FIG. 8, a method of creating an enriched reagent is illustrated. Enriching the reagent by mixing the liquid reagent with an enriching agent creates an enriched lyophilized reagent with better adherence characteristics. Thus, when the enriched reagent is lyophilized, the enhanced adherence creates a stronger bond between the lyophilized reagent cake and the side wall of the reagent cartridge. The enhanced reagent may be used with any of the reagent cartridges described herein to further reduced the chances of the lyophilized reagent cake from becoming dislodged from the inner surface of the reagent cartridge side wall a reagent cartridge for a library preparation system includes a cartridge body having a side wall, an opening at a first end, the cartridge body being closed at a second end. In some implementations, the enriching agent comprises polyethylene glycol (PEG).Rehydratinq Lyophilized Reagent CakesHydrophilic / Hydrophobic coatings

[0085] Turning now to FIG. 9A and FIG. 9B, in another implementation, a reagent cartridge 154 for a library preparation system includes a cartridge body 160 having a side wall 162, and an opening 164 at a first end 166, the cartridge body 160 being closed at a second end 168. The cartridge body 160 comprises a hydrophilic coating 182 in a hydrophilic region 184 and a hydrophobic coating 186 in a hydrophobic region 188 on an inner surface of the cartridge body side wall 162. A lyophilized reagent 170 is disposed in the cartridge body 160.

[0086] In one example, as illustrated on the left side of FIG. 9A, the hydrophobic coating 186 is disposed at least partially between the opening 164 and the hydrophilic coating 182.

[0087] In yet another example, as illustrated on the right side of FIG. 9A, a hydrophilic guide 190 extends from the hydrophilic region 184 to the opening 164.

[0088] By incorporating hydrophilic coatings 182 and hydrophobic coatings 186 in strategic locations on the inner surface of the reagent cartridge wall 162, rehydrating liquid can be directed into contact with the location of the lyophilized reagent 170, which enhances complete rehydration and mixing and reduces loss of reagent material.

[0089] Turning now to FIG. 10, in some implementations, the hydrophilic coating 182 comprises a lubricant 192. In some implementations, the lubricant comprises oil.Cartridge cross-sectional shape

[0090] Turning now to FIGS. 11 A and 11 B, yet another implementation of a reagent cartridge for a library preparation system illustrated. In FIGS. 11 A and 11 B, an array of reagent cartridges 154 is illustrated. Each reagent cartridge 154 includes a cartridge body 160 having a side wall, an opening at a first end, the cartridge body being closed at a second end. The cartridge body 160 has a non-circular cross-sectional shape, as illustrated by the openings 164 in FIGS. 11 A and 11 B. A lyophilized reagent (not shown) is disposed in the cartridge body 160.

[0091] In some examples , the non-circular cross-sectional shape is a substantially square-shape. In other implementations, the non-circular cross-sectional shape is a substantially diamond-shape. In yet other implementations, the non-circular cross-sectional shape is a substantially oval-shape. In yet other implementations, the substantially ovalshape includes a secondary smaller oval-shaped lobe.

[0092] The non-circular shapes help reduce the surface tension in the reagent cartridges. The non-circular shapes also reduce air bubble trapping, which enhances rehydration mixing with lyophilized reagent cakes.Extracting Liquid Reagent from Reagent Cartridges

[0093] Aspirating tip / well cooperation to raise liquid level

[0094] Turning now to FIGS. 12A and 12B, in another implementation, a reagent cartridge 154 for a library preparation system includes a cartridge body 160 having a side wall 162, and an opening 164 at a first end 166, the cartridge body 160 being closed at a second end 168. The cartridge body 160 is sized and shaped to cooperate with an aspiratortip 194 so that the aspirator tip 194 fills more than 90% of the volume of the cartridge body 160 when the aspirator tip 194 is fully inserted into the cartridge body 160. A liquid reagent 170 is disposed in the cartridge body 160.

[0095] The aspirator tip 194 causes the reagent within the cartridge body 160 to rise more than 50% higher than a level of reagent in the cartridge body 160 without the aspirator tip 194 fully inserted, which allows a higher percentage of the liquid reagent 170 to be aspirated from the cartridge body 160.

[0096] In some examples, the shape of an outer surface of the aspirator tip 194 is complementary to the shape of an inner surface of the reagent cartridge body 160, which allows the aspirator tip 194 to extend further into the interior volume of the cartridge body 160.Well deformable end

[0097] Turning now to FIGS. 13A and 13B, yet another implementation of a reagent cartridge 154 for a library preparation system is illustrated. The reagent cartridge 154 includes a cartridge body 160 having a side wall 162, and an opening 164 at a first end 166, the cartridge body 160 being closed at a second end 168. The cartridge body 160 includes a deformable portion 196 proximate the closed second end 168 . A liquid reagent 170 is disposed in the cartridge body 160.

[0098] The deformable portion 196 deforms inwardly to reduce the interior volume of the cartridge body 160 proximate the deformable portion 196, as illustrated in FIG. 13B.When the deformable portion 196 deforms inwardly, a surface level of the liquid reagent 170 rises within the interior volume of the cartridge body 160. As a result, a higher percentage of the liquid reagent 170 may be aspirated from the cartridge body 160.

[0099] The foregoing description is provided to enable a person skilled in the art to practice the various configurations described herein. While the subject technology has been particularly described with reference to the various figures and configurations, it should be understood that these are for illustration purposes only and should not be taken as limiting the scope of the subject technology.

[0100] As used herein, an element or step recited in the singular and proceeded with the word “a” or “an” should be understood as not excluding plural of said elements or steps, unless such exclusion is explicitly stated. Furthermore, references to “one implementation” are not intended to be interpreted as excluding the existence of additional implementations that also incorporate the recited features. Moreover, unless explicitly stated to the contrary, implementations “comprising,” “including,” or “having” an element or a plurality of elementshaving a particular property may include additional elements whether or not they have that property. Moreover, the terms “comprising,” including,” having,” or the like are interchangeably used herein.

[0101] The terms “substantially," "approximately," and “about” used throughout this Specification are used to describe and account for small fluctuations, such as due to variations in processing. For example, they can refer to less than or equal to ±5%, such as less than or equal to ±2%, such as less than or equal to ±1%, such as less than or equal to ±0.5%, such as less than or equal to ±0.2%, such as less than or equal to ±0.1%, such as less than or equal to ±0.05%. In one example, these terms may include situation where there is no variation - 0%.

[0102] There may be many other ways to implement the subject technology. Various functions and elements described herein may be partitioned differently from those shown without departing from the scope of the subject technology. Various modifications to these implementations may be readily apparent to those skilled in the art, and generic principles defined herein may be applied to other implementations. Thus, many changes and modifications may be made to the subject technology, by one having ordinary skill in the art, without departing from the scope of the subject technology. For instance, different numbers of a given module or unit may be employed, a different type or types of a given module or unit may be employed, a given module or unit may be added, or a given module or unit may be omitted.

[0103] Underlined, bold, and / or italicized headings and subheadings are used for convenience only, do not limit the subject technology, and are not referred to in connection with the interpretation of the description of the subject technology. All structural and functional equivalents to the elements of the various implementations described throughout this disclosure that are known or later come to be known to those of ordinary skill in the art are expressly incorporated herein by reference and intended to be encompassed by the subject technology. Moreover, nothing disclosed herein is intended to be dedicated to the public regardless of whether such disclosure is explicitly recited in the above description.

[0104] It should be appreciated that all combinations of the foregoing concepts and additional concepts discussed in greater detail below (provided such concepts are not mutually inconsistent) are contemplated as being part of the subject matter disclosed herein. In particular, all combinations of claimed subject matter appearing at the end of this disclosure are contemplated as being part of the subject matter disclosed herein.

Claims

CLAIMSWhat is claimed is:1 . A reagent cartridge for a library preparation system, the reagent cartridge comprising: a cartridge body having a side wall, and an opening at a first end, the cartridge body being closed at a second end; and a lyophilized reagent disposed in the cartridge body, wherein the cartridge body has a high height to width aspect ratio.

2. The reagent cartridge of claim 1 , wherein the height to width aspect ratio is greater than 3:1 .

3. The reagent cartridge of claim 1 or claim 2, wherein the height to width aspect ratio is greater than 5:1.

4. The reagent cartridge of any one of claims 1 -3, wherein at least part of the cartridge body is substantially cylindrical.

5. The reagent cartridge of any one of claims 1 -3, wherein at least part of the cartridge body is substantially conical.

6. The reagent cartridge of claim 5, wherein the conical part of the cartridge body narrows from top to bottom.

7. The reagent cartridge of claim 5, wherein the cartridge body narrows from bottom to top.

8. The reagent cartridge of claim 5, wherein the cartridge body includes two substantially conical parts that join together to form a substantially hour-glass shape.

9. A reagent cartridge for a library preparation system, the reagent cartridge comprising: a cartridge body having a side wall, and an opening at a first end, the cartridge body being closed at a second end; and a lyophilized reagent disposed in the cartridge body, wherein the cartridge body has a non-cylindrical shape.

10. The reagent cartridge of any one of claim 9, wherein at least part of the cartridge body is substantially conical.11 . The reagent cartridge of claim 9 or 10, wherein the cartridge body narrows from top to bottom.

12. The reagent cartridge of claim 9 or 10, wherein the cartridge body narrows from bottom to top.

13. The reagent cartridge of claim 9 or 10, wherein the cartridge body includes two substantially conical parts that join together to form a substantially hour-glass shape.

14. A reagent cartridge for a library preparation system, the reagent cartridge comprising: a cartridge body having a side wall, and an opening at a first end, the cartridge body being closed at a second end; and a lyophilized reagent disposed in the cartridge body, wherein the cartridge body has an internal roughened surface.

15. The reagent cartridge of claim 14, wherein the roughened surface is part of the cartridge body side wall.

16. The reagent cartridge of claim 14, wherein the roughened surface is formed by a coating on the cartridge body side wall.

17. The reagent cartridge of claim 14, wherein the roughened surface does not affect optical properties of the cartridge body side wall.

18. A reagent cartridge for a library preparation system, the reagent cartridge comprising: a cartridge body having a side wall, and an opening at a first end, the cartridge body being closed at a second end; and a lyophilized reagent disposed in the cartridge body, wherein the cartridge body has an internal projection.

19. The reagent cartridge of claim 18, wherein the internal projection is a single ledge extending inward from an inner surface of the cartridge body side wall.

20. The reagent cartridge of claim 19, wherein the internal projection is annular in shape.21 . The reagent cartridge of claim 19 or claim 20 further comprising a plurality of internal projections.

22. The reagent cartridge of claim 21 , wherein the plurality of internal projections extend in a height direction along the cartridge body side wall.

23. A reagent cartridge for a library preparation system, the reagent cartridge comprising: a cartridge body having a side wall, and an opening at a first end, the cartridge body being closed at a second end; and a lyophilized reagent disposed in the cartridge body, wherein the cartridge body side wall comprises a hydrophobic coating.

24. The reagent cartridge of claim 23, wherein the hydrophilic coating is 4 pm or less.

25. The reagent cartridge of claim 23, wherein the hydrophilic coating is 2 pm or less.

26. The reagent cartridge of any one of claims 23-25, wherein the hydrophilic coating comprises polydimethylsiloxane.

27. A reagent cartridge for a library preparation system, the reagent cartridge comprising: a cartridge body having a side wall, and an opening at a first end, the cartridge body being closed at a second end; and an enriched lyophilized reagent disposed in the cartridge body, wherein the enriched lyophilized reagent comprises a reagent and an enriching agent.

28. The reagent cartridge of claim 27, wherein the enriching agent comprises Polyethylene glycol (PEG).

29. A reagent cartridge for a library preparation system, the reagent cartridge comprising: a cartridge body having a side wall, and an opening at a first end, the cartridge body being closed at a second end; and a lyophilized reagent disposed in the cartridge body, wherein the cartridge body comprises a hydrophilic coating in a hydrophilic region and a hydrophobic coating in a hydrophobic region on an inner surface of the cartridge body side wall.

30. The reagent cartridge of claim 29, wherein the hydrophobic coating is disposed at least partially between the opening and the hydrophilic coating.31 . The reagent cartridge of either claim 29 or claim 30, further comprising a hydrophilic guide that extends from the hydrophilic region to the opening.

32. The reagent cartridge of any one of claims 29-31 , wherein the hydrophilic coating comprises a lubricant.

33. The reagent cartridge of claim 32, wherein the lubricant comprises oil.

34. A reagent cartridge for a library preparation system, the reagent cartridge comprising: a cartridge body having a side wall, and an opening at a first end, the cartridge body being closed at a second end; and a lyophilized reagent disposed in the cartridge body, wherein the cartridge body has a non-circular cross-sectional shape.

35. The reagent cartridge of claim 34, wherein the non-circular cross-sectional shape is a substantially square-shape.

36. The reagent cartridge of claim 34, wherein the non-circular cross-sectional shape is a substantially diamond-shape.

37. The reagent cartridge of claim 34, wherein the non-circular cross-sectional shape is a substantially oval-shape.

38. The reagent cartridge of claim 37, wherein the substantially oval-shape includes a secondary smaller oval-shaped lobe.

39. A reagent cartridge for a library preparation system, the reagent cartridge comprising: a cartridge body having a side wall, and an opening at a first end, the cartridge body being closed at a second end; and a liquid reagent disposed in the cartridge body, wherein the cartridge body is sized and shaped to cooperate with an aspirator tip so that the aspirator tip fills more than 90% of the volume of the cartridge body when the aspirator tip is fully inserted into the cartridge body.

40. The reagent cartridge of claim 39, wherein the aspirator tip causes the reagent within the cartridge body to rise more than 50% higher than a level of reagent in the cartridge body without the aspirator tip fully inserted.41 . The reagent cartridge of claim 39 of claim 40, wherein the shape of an outer surface of the aspirator tip is complementary to the shape of an inner surface of the reagent cartridge body.

42. A reagent cartridge for a library preparation system, the reagent cartridge comprising: a cartridge body having a side wall, and an opening at a first end, the cartridge body being closed at a second end; and a liquid reagent disposed in the cartridge body, wherein the cartridge body includes a deformable portion proximate the closed second end.

43. The reagent cartridge of claim 42, wherein the deformable portion deforms inwardly to reduce the interior volume of the cartridge body proximate the deformable portion.

44. The reagent cartridge of claim 42 or 43, wherein a surface level of the liquid reagent rises within the interior volume when the deformable portion deforms inwardly.

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