Flexible capillary array devices and related systems and methods

Abstract

The capillary array device includes a flexible component that allows movement of at least a portion of the device relative to an array of capillaries, thereby allowing different materials to be loaded into the capillaries, which may be utilized to contain samples to be measured by a capillary electrophoresis (CE) instrument or other type of analytical instrument.

Description

[Technical Field]

[0001] [Related Applications] This application claims the benefit under 35 U.S.C. § 119(e) of U.S. Provisional Patent Application No. 63 / 388,593, filed July 12, 2022, entitled "FLEXIBLE CAPILLARY ARRAY DEVICE AND RELATED SYSTEMS AND METHODS," the entire contents of which are incorporated herein by reference.

[0002] The present invention generally relates to a capillary array device for holding a parallel arrangement of multiple capillaries. In particular, the present invention relates to a capillary array device having a flexible component that allows movement of a portion of the device relative to the multiple capillaries. The multiple capillaries can be used to contain samples to be detected or measured by optical-based instruments. The multiple capillaries can be used, for example, for capillary electrophoresis (CE). [Background technology]

[0003] Analytical instruments often utilize multiple capillaries (i.e., multiple tubes with micrometer-scale pores) to contain and transport sample-containing fluids (either in liquid or gas phase) for various purposes. In some analytical instruments, a capillary (or at least an optically transparent section of the capillary, referred to as a capillary window) can be utilized as a sample detection cell. In this case, the analytical instrument is configured to perform optical-based measurements (e.g., fluorescence, absorbance, imaging, etc.) of analytes (i.e., sample components of interest, such as chemical or biological compounds) of a sample contained within the capillary by reading electromagnetic energy emitted from the sample. Such emission can be in response to the sample being illuminated by a beam of electromagnetic energy directed toward the capillary (window) by a light source in the analytical instrument. In some analytical instruments, the capillary can contain within its lumen (internal bore) a separation medium configured to separate different analytes of the sample based on different properties or attributes, such as molecular size, molecular composition, or charge. In some analytical techniques, the separation medium may be stationary (i.e., stationary phase) within the capillary. In this case, the sample is carried by a fluid (i.e., a mobile phase, such as one or more solvents) through the capillary and in contact with the separation medium. As the sample migrates through the separation medium, different analytes of the sample become separated from one another, thereby facilitating detection / measurement of the analytes by an analytical instrument. Examples of analytical separation techniques include capillary electrophoresis (CE, particularly capillary gel electrophoresis or CGE), liquid chromatography (LC), and gas chromatography (GC).

[0004] Sample analysis can be enhanced by operating multiple capillaries (or their capillary windows) in parallel, with each capillary containing an individual sample, in which case the analytical instrument can be configured to read out, or additionally illuminate, multiple capillaries simultaneously. Summary of the Invention [Problem to be solved by the invention]

[0005] Many of the components of CE systems or other analytical separation systems can be realized on the microfluidics scale, meaning that one or more dimensions of such components are on the micrometer scale, or additionally, other dimensions are on the millimeter scale. Thus, many of these components can be embodied in or coupled to one or more microfluidic chips. Typically, the conduits (and chambers or other enclosed spaces) provided for transporting fluids are channels formed between the glass layers of the microfluidic chip. Such microfluidic chips are often fabricated from glass using glass etching and glass bonding techniques. Fabrication of these microfluidic chips is expensive, and microfluidic chip designs are limited by their available fabrication techniques (e.g., 2.5D design limitations due to the required etching steps). Additionally, complex procedures are often required to prepare microfluidic chips for use with analytical instruments. Such procedures may include priming the fluid conduits and chambers of the microfluidic chip with fluids (e.g., by operating a priming station external to the analytical instrument) and transporting liquids and gels to the microfluidic chip by operating a fluid handling system involving various liquid or gel reservoirs, tubing, pumps, valves, etc. Additionally, multiple capillaries are often pre-filled with analytical separation media (e.g., CE gel, chromatographic stationary phases, etc.), which leads to problems associated with limited shelf life and degradation of the analytical separation media.

[0006] There is currently a need to provide a capillary array device that overcomes problems such as those noted above and / or provides other advantages in the performance of analytical runs on samples within the capillaries. [Means for solving the problem]

[0007] To solve, in whole or in part, the problems described above and / or other problems that may have been observed by those skilled in the art, the present disclosure provides methods, processes, systems, apparatus, instruments, and / or devices, as illustrated by way of example in the implementations set forth below.

[0008] According to one embodiment, a capillary array device includes a capillary array holder having a stationary section (immovable section, fixed section), a movable section, and a flexible section (flexible section) connecting the stationary section and the movable section, and a plurality of capillaries attached to the capillary array holder, the plurality of capillaries being arranged in parallel and extending along the device axis of the capillary array holder, wherein the movable section is linearly movable along the device axis relative to the plurality of capillaries and the stationary section, and the flexible section deforms in response to movement of the movable section.

[0009] In one embodiment, the capillary array device further includes a voltage source configured to apply a potential difference across the plurality of capillaries.

[0010] In one aspect, the voltage source is configured to apply a potential difference according to operating parameters effective to perform capillary electrophoresis on samples disposed in the plurality of capillaries.

[0011] According to another aspect, a sample analysis system includes a capillary array device according to any of the aspects disclosed herein and a photodetector positioned in optical alignment with the capillaries to receive light emitted from the plurality of capillaries.

[0012] In one aspect, the sample analysis system further includes a voltage source configured to apply a potential difference across the plurality of capillaries.

[0013] In one aspect, the voltage source is configured to apply a potential difference according to operating parameters effective to perform capillary electrophoresis on samples disposed in the plurality of capillaries.

[0014] According to another aspect, a method for injecting a liquid or gel into a plurality of capillaries includes the steps of: providing a capillary array device comprising a plurality of capillaries and a capillary array holder, wherein the capillary array holder comprises a stationary section, a movable section, and a flexible section connecting the stationary section and the movable section, and wherein the plurality of capillaries are attached to the capillary array holder and arranged in parallel, extending along a device axis of the capillary array holder; moving the movable section along the device axis to a position where the plurality of capillaries extend into one or more receptacles of the capillary array holder, wherein the liquid or gel is contained in the one or more receptacles and the flexible section deforms in response to movement of the movable section; and injecting the liquid or gel from the one or more receptacles into the plurality of capillaries by capillary action.

[0015] In one aspect, the plurality of receptacles respectively contain samples to be analyzed, and the injecting step includes injecting the plurality of samples into the plurality of capillaries respectively.

[0016] In one aspect, the method further includes, after the injecting step, applying a voltage across each of the plurality of capillaries along the device axis, the voltage being applied according to operating parameters effective to perform capillary electrophoresis on the sample.

[0017] According to another aspect, a method for analyzing a sample includes injecting a liquid or gel into a plurality of capillaries according to any of the aspects disclosed herein, wherein the liquid or gel includes a sample to be analyzed, and the injecting step includes injecting the sample into each of the plurality of capillaries; and performing optical measurements of the sample in the plurality of capillaries to obtain optical data from one or more analytes in the sample.

[0018] In one aspect, the method further comprises the step of analytically separating the sample in each capillary before and / or during the optical measurements.

[0019] In one embodiment, analytical separation of a sample comprises performing capillary electrophoresis on the sample.

[0020] Other devices, apparatus, systems, methods, features, and advantages of the invention will be, or become, apparent to one with skill in the art upon examination of the following figures and detailed description. All such additional systems, methods, features, and advantages are intended to be included within this description, be within the scope of the invention, and be protected by the accompanying claims.

[0021] The present invention may be better understood by reference to the following figures, in which components are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the invention, in which like reference numbers indicate corresponding parts throughout the different views. [Brief explanation of the drawings]

[0022] [Figure 1A] 1 is a top plan view of an example of a capillary array device according to an embodiment of the present disclosure shown in a first position. [Figure 1B] 1B is a top plan view of the capillary array device illustrated in FIG. 1A shown in a second position. [Figure 1C]FIG. 1B is a top plan view of the capillary array device illustrated in FIG. 1A shown in a third position. [Figure 1D] 1B is a longitudinal side view of the capillary array device illustrated in FIG. 1A shown coupled to an actuator according to an embodiment of the present disclosure. [Figure 1E] 1B is a longitudinal side view of the capillary array device illustrated in FIG. 1A shown coupled to an electrical circuit according to an embodiment of the present disclosure. [Figure 1F] 1B is a longitudinal side view of the capillary array device illustrated in FIG. 1A shown coupled to an optical-based measurement device according to an embodiment of the present disclosure. [Figure 2] 1B is an exploded view of an example of a capillary array device and device support illustrated in FIG. 1A according to an embodiment of the present disclosure. [Figure 3] FIG. 10 is a longitudinal side view of another example of a capillary array device according to another embodiment of the present disclosure. [Figure 4A] FIG. 10 is a top perspective view of another example of a capillary array device according to another embodiment of the present disclosure. [Figure 4B] FIG. 4B is a top plan view of the capillary array device illustrated in FIG. 4A. [Figure 4C] 4B is a cutaway top perspective view of the capillary array device illustrated in FIG. 4A taken along line AA shown in FIG. 4B. [Figure 4D] 4B is a cutaway longitudinal side view of the capillary array device illustrated in FIG. 4A taken along line AA shown in FIG. 4B. [Figure 4E] 4B is a top plan view of the capillary array device illustrated in FIG. 4A shown in a first position. [Figure 4F] 4B is a top plan view of the capillary array device illustrated in FIG. 4A shown in a first position. [Figure 4G] 4B is a top plan view of the capillary array device illustrated in FIG. 4A shown in a first position. [Figure 5A] FIG. 10 is a top perspective view of another example of a capillary array device according to another embodiment of the present disclosure. [Figure 5B]FIG. 5B is a top plan view of the capillary array device illustrated in FIG. 5A. [Figure 6A] FIG. 10 is a top perspective view of another example of a capillary array device according to another embodiment of the present disclosure. [Figure 6B] FIG. 6B is a top plan view of the capillary array device illustrated in FIG. 6A. [Figure 7A] FIG. 10 is a longitudinal side view of another example of a capillary array device according to another embodiment of the present disclosure, shown in an inactivated position. [Figure 7B] FIG. 7B is a longitudinal side view of the capillary array device illustrated in FIG. 7A shown in the operating position. [Figure 8] 1 is a schematic diagram of an example of a sample analysis system according to an embodiment of the present disclosure. DETAILED DESCRIPTION OF THE INVENTION

[0023] All illustrations in the depicted figures are considered to be schematic unless specifically indicated otherwise.

[0024] In this disclosure, all described "aspects," "examples," and "embodiments" are considered to be non-limiting and non-exclusive. Thus, the explicit description of a particular "aspect," "example," or "embodiment" herein does not exclude other "aspects," "examples," and "embodiments" from the scope of the disclosure, even if not explicitly described. In this disclosure, the terms "aspects," "examples," and "embodiments" are used synonymously, i.e., are considered to have interchangeable meanings.

[0025] In this disclosure, the terms "substantially," "approximately," or "about," when modifying a specified numerical value, may be considered to encompass a range of values including + / - 10% of such numerical value.

[0026] In the context of this disclosure, the term "light" refers to electromagnetic energy (i.e., photons) in a general sense and is therefore not limited to electromagnetic energy in the visible range. Depending on the embodiment, the wavelength range transmitted to or emitted from the capillary may be in the ultraviolet range, the visible range, the infrared range, or a combination or overlap of two or more of these ranges. In the context of this disclosure, the ultraviolet range is considered to extend from 10 nanometers (nm) to 400 nm, the visible range is considered to extend from 400 nm to 700 nm, and the infrared range is considered to extend from 700 nm to 1000 nm (1 millimeter (mm)), recognizing that the aforementioned ranges may vary slightly and / or overlap slightly depending on the technical basis relied upon for reference or definition.

[0027] 1A-1F illustrate a non-exclusive example of a capillary array device 100 according to an embodiment of the present disclosure. For purposes of reference and explanation, FIGS. 1A-1F (and other depictions) include an arbitrarily positioned Cartesian coordinate (xyz) system. The x-axis, y-axis, and z-axis are also referred to herein as the device axis (or capillary axis), horizontal axis, and elevation axis (height axis), respectively. The xy-plane is also referred to herein as the device plane (or capillary plane). The yz-plane is also referred to herein as the horizontal plane. Dimensions along the x-axis, y-axis, and z-axis are considered to be length, width, and height (or thickness), respectively. Also for purposes of reference and explanation, the xy-plane is assumed to be horizontal with respect to the ground (i.e., the surface on which the capillary array device 100 or the instrument on which the capillary array device 100 is installed rests), and the z-axis is assumed to be vertical (plumb). More generally, however, the capillary array device 100 is not limited to any particular orientation with respect to ground. In the context of this disclosure, the term "axial" refers to the device axis (x-axis) unless otherwise specified or the context indicates otherwise.

[0028] 1A is a top plan view of a capillary array device 100. In this example, the capillary array device 100 generally has a generally flat geometry (i.e., shaped as a plate, chip, etc.) and extends along a device axis (x-axis). That is, the largest overall dimension of the capillary array device 100 is its length, although the capillary array device 100 is not limited to such a geometry. Generally, the capillary array device 100 has a first axial end 104 and an axially opposite second axial end 108, which together define the overall length of the capillary array device 100. The capillary array device 100 further has an upper side 112 and a lower side 116 (FIG. 1D) that lie in the device (xy) plane. In the context of this disclosure, the terms "upper" and "lower" are merely relative to one another to distinguish one from the other and are not intended to limit the capillary array device 100 to any particular orientation relative to the ground or any other reference datum.

[0029] Generally, the capillary array device 100 includes a capillary array holder 120 and a plurality of capillaries 124. The capillary array holder 120 is configured to securely hold the plurality of capillaries 124 in a parallel arrangement. In this arrangement, the plurality of capillaries 124 extend along the device axis, are spaced apart from one another along the transverse axis, and are held in fixed positions and at fixed distances from one another. To this end, the capillary array holder 120 may include a plurality of grooves or channels at various locations (not shown, but described further below) that can receive the capillaries 124 and guide relative movement between (parts of) the capillary array holder 120 and the plurality of capillaries 124, as described below. In this example, four capillaries 124 are provided, but the capillary array device 100 may include any number of capillaries 124.

[0030] The capillary array holder 120 is defined by a structural frame or body of material. The body may be a single piece (monolithic) or may include two or more pieces attached (e.g., glued, attached, welded, etc.) or fastened (secured) together (e.g., mechanically). The (body of) the capillary array holder 120 may include one or more stationary sections 128, one or more movable sections 132, and one or more flexible sections (or flexible joints) 136 coupled to the stationary sections 128 and / or movable sections 132. The stationary sections 128 are configured to be fixed in place, such as by being appropriately attached to a device support or receptacle that is part of, or alternatively attached to, the associated analytical instrument. The movable sections 132 are configured to have at least one degree of freedom of movement, particularly along a device axis, that can be enabled and guided by an appropriately configured device support. The double-headed arrows in FIG. 1A depict the linear movement of the multiple capillaries 124 and the movable section 132 alternately toward and away from the stationary section 128 .

[0031] The stationary section 128 and the movable section 132 may generally be configured as a primarily solid body of material. Depending on the embodiment, the stationary section 128 and the movable section 132 may include various features provided (formed, machined, applied, etc.) on, in, or through their body, for example, to hold or conduct liquids or gels, support or guide capillaries, accommodate or define paths for light transmission, attach to a device support, engage actuators, communicate with electrical circuitry, provide identification or other information for the capillary array holder 120, etc.

[0032] The flexible section 136 is configured to allow the movable section 132 to move, particularly to translate linearly along the device axis, relative to the plurality of capillaries 124 and the stationary section 128. To this end, the flexible section 136 is configured to flex (or deform, expand, etc.) in response to the movement of the movable section 132. Depending on the configuration, this "flexing" may involve movement (movement) of one or more portions of the flexible section 136 in one or more directions, and even compression and / or expansion / extension (e.g., stretching). In the context of the present disclosure, the flexible section 136 is "flexible" (or has a "flexible" configuration) relative to the movable section 132 (or relative to both the movable section 132 and the stationary section 128). In other words, the movable section 132 (or both the movable section 132 and the stationary section 128) is "rigid" relative to the flexible section 136. The flexible section 136 is "flexible" in the sense that it is softer or more compliant (or less compliant) than the stationary section 128 and / or the movable section 132 to which it is attached. In other words, in response to an applied (actuation) force, the flexible section 136 will readily yield to the applied force by "flexing" and will not transfer a significant amount of the applied force to the stationary section 128, while the movable section 132 will not flex but will instead move towards (in the direction of) the flexible section 132 and will transfer all or most of the applied force to the flexible section 132.

[0033] In some embodiments of the flexible configuration, the flexible region 136 can have an “open frame” configuration (not shown in FIGS. 1A-1F but illustrated by the examples below). Such an open frame configuration can be a primary contributor to the flexibility of the flexible region 136 when compared to the inherent flexibility (pliability) of the solid material of the flexible region 136. In an open frame configuration, the three-dimensional space occupied by the flexible region 136 can be primarily open space instead of solid material, particularly when compared to the stationary region 128 and the movable region 132. Most of the three-dimensional space occupied by the stationary region 128 and the movable region 132 is solid material, which makes the stationary region 128 and the movable region 132 structurally more rigid (less flexible and less compliant) and stronger or more robust, and therefore more resistant to deformation (and less responsive to applied forces), than the flexible region 136. In comparison, a large percentage of the three-dimensional space occupied by flexible section 136 is open space. As examples of "predominantly open space" or "large percentage of open space," the percentage of the three-dimensional space occupied by flexible section 136 that is open space can be greater than 30%, or greater than 50%, or greater than 70%.

[0034] The open frame configuration may be achieved by an arrangement (array, pattern, etc.) of multiple open spaces formed within and / or through the solid portion of the flexible section 136. In other words, the open frame configuration may be achieved by structuring the body of the flexible section 136 to define an arrangement of multiple open spaces. By way of example, the flexible section 136 may include an arrangement of multiple holes (openings) passing through the solid portion of the flexible section 136 in one or more directions (x-axis, y-axis, and / or z-axis). The multiple holes may have any size and shape (circular, oval, linear, polygonal, diamond-shaped, etc.) effective to achieve the degree of flexibility (flexibility) required for a given embodiment. The plurality of holes may be defined by an arrangement of a plurality of "thin" structural members or compliant beams (e.g., webs, meshes, grids, porous bodies, etc., formed by a plurality of ribs, arms, walls, rods, beams, etc.), some of which are integral with each other and some of which are additionally integral with or attached to the stationary area 128 or the movable area 132. In the context of the present disclosure, a "thin" structural member has at least one dimension that is significantly smaller than the length, width, and height of the movable area 132 (or additionally the stationary area 128). As a non-exclusive example, a "thin" structural member may have a width in a particular plane (e.g., the device plane) that is no more than 20%, 40%, or 60% of the length, width, and height of the movable area 132 (or additionally the stationary area 128). 4A-6B , the plurality of holes may be open cells dispersed throughout the bulk material of the flexible region 136, such as open-cell foam or memory foam (e.g., polyurethane (PU) foam or polyethylene terephthalate (PET) foam).

[0035] Because the open-frame configuration (and the compliance of its structural members) allows the flexible section 136 to be flexible, in such embodiments, the flexible section 136 can be made of a variety of materials, and can even be made of the same material as the stationary section 128 or the movable section 132. Such a configuration allows the capillary array holder 120 (including the stationary section 128, the movable section 132, and the flexible section 136) to be fabricated as a single-piece article, using techniques appropriate for the materials selected and the features to be formed. Examples of materials for the flexible section 136 (or the entire capillary array holder 120) include, but are not limited to, metals (e.g., aluminum, nickel, copper), metal alloys (e.g., stainless steel), silicon, ceramics, glass, and polymers or plastics. Examples of polymers or plastics include, but are not limited to, polydimethylsiloxane (PDMS), polyoxymethylene (POM), liquid crystal polymer (LCP), polyacrylamide (PA), polycarbonate (PC), poly(methyl methacrylate) (PMMA), polyether ether ketone (PEEK), polyethylene terephthalate (PET), polyethylene (PE), polystyrene (PS), polymethyl methacrylate (PMMA), polyvinyl chloride (PVC), polypropylene (PP), polyphenylene sulfide (PPS), and mixtures of two or more of the above materials. For example, the mixture may be a two-component polymer mold with conductive carbon fiber-filled segments overmolded with an insulating polymer, thereby creating an integrated high-voltage (HV) electrode within the polymer housing.

[0036] In another example of a flexible configuration, the flexible region 136 does not necessarily have an open-frame configuration as described above, but can be made of a material that is inherently fairly flexible (pliable). In this case, the stationary region 128 and the movable region 132 can be made of different materials that are less flexible than the material of the flexible region 136. In this context, the term "fairly flexible" refers to the flexibility of the stationary region 128 and the movable region 132. For example, in response to an applied (actuation) force, the flexible region 136, due to its fair flexibility, easily flexes (moves with compression and / or expansion / extension), while the stationary region 128 and the movable region 132 do not flex (at least to any significant degree). Examples of fairly flexible materials for the flexible region 136 include, but are not limited to, metal alloys such as spring steel, semi-crystalline polymers such as PE, PP, PA, POM, and polybutylene terephthalate (PBT), and amorphous polymers such as PC, acrylonitrile butadiene styrene (ABS), PS, and PVC.

[0037] In other examples of flexible configurations, the flexible section 136 can include one or more hinges or other types of components that define a pivot axis. Each hinge can connect two subsections of the flexible section 136, allowing one or both of the two subsections to pivot about the pivot axis in response to a force. For example, the flexible section 136 shown in Figures 1A-1C can include one or more hinges with a pivot axis in the z-direction.

[0038] In other embodiments, the capillary array holder 120 may include an intrinsic actuator. For example, all or a portion of the movable section 132 and / or the flexible section 136 may be an intrinsic actuator, or an intrinsically actuated component (i.e., may be made of an intrinsically actuated material). Similarly, the movable section 132 and / or the flexible section 136 may include an intrinsically actuated component that is in contact with or coupled to a non-intrinsically actuatable component (i.e., a component that is not itself an intrinsic actuator). In other words, in either case, the movable section 132 and / or the flexible section 136 may be or include an intrinsically actuated component. Generally, an intrinsically actuated material is a material that can reversibly change its shape (or be deformed) in at least one dimension in response to receiving an energy stimulus (or activation) applied thereto, such as an electrical input (voltage or electric field), a thermal input (heat), an electromagnetic input (light), or a magnetic input (magnetic field). Specific types and material compositions of internally actuated components are currently known or may be later developed, such as in the field of "soft" robotics. Examples of internally actuated components include, but are not limited to, dielectric elastomer actuators (DEAs), shape memory polymers (SMPs), and shape memory alloys (SMAs).

[0039] DEAs can be configured as compliant, flat-plate capacitors, in which a body or block of internally actuated (DEA) material is sandwiched between two flat (plate, layer, film, coating, etc.) electrodes (or alternatively, two ionic hydrogels, such as polyacrylamide gels). The electrodes are coupled to a high-voltage (HV) source, which can be the same HV sources utilized for electrophoresis and are described herein. Upon application of a high voltage (i.e., a high-voltage electric field) between the electrodes, the DEA material is effectively placed in tension such that the DEA material is compressed (i.e., its thickness is reduced) between the electrodes by the electrostatic voltage and concomitantly expanded in a plane parallel to the electrodes. The amount of electrostatic voltage generated depends on the magnitude of the applied voltage, the thickness of the DEA material, and the dielectric constant of the DEA material. Thus, for example, if all or a portion of movable area 132 and / or flexible area 136 are comprised of a DEA material, the DEA material and associated electrodes can be positioned and oriented such that application of a high voltage causes movable area 132 and / or flexible area 136 to contract (contract) along the device axis. In another example, if a DEA component is separate from (but in contact with or coupled to) movable area 132 and / or flexible area 136 (or equivalently, movable area 132 and / or flexible area 136 includes a DEA component as well as a non-internally actuatable component), the DEA component (DEA material and associated electrodes) can be positioned and oriented such that electric field-induced contraction or contraction causes the DEA component to push or pull movable area 132 and / or flexible area 136 along the device axis. Examples of DEA materials include, but are not limited to, acrylic elastomers (e.g., VHB4910 elastomer available from 3M, St. Paul, Minnesota, USA), silicones (e.g., PDMS), and natural rubbers (e.g., polyisoprene elastomers, or latex).

[0040] In a typical example, an SMP can be pre-strained (pre-stretched) into a deformed shape by applying thermal energy, specifically by heating the SMP to a temperature above its glass or melt transition temperature, and then cooled to retain the deformed shape. Subsequently, upon another application of thermal energy, the deformed SMP will return to its original (undeformed) shape due to the release of the strain. Thus, like a DEA component, if all or part of the movable section 132 and / or flexible section 136 are made of an SMP material, the SMP component can be positioned and oriented such that application of thermal energy will return the deformed movable section 132 and / or flexible section 136 to its or their original shape. Alternatively, if the SMP components are separate from (but in contact with or coupled to) the movable region 132 and / or flexible region 136 (or, equivalently, the movable region 132 and / or flexible region 136 include SMP components as well as non-internally actuatable components), the SMP components can be positioned and oriented such that a heat-induced shape change causes the SMP components to push or pull the movable region 132 and / or flexible region 136 along the device axis. Examples of heat-activated SMP materials include, but are not limited to, polyurethane (PU), polyethylene oxide (PEO), PS, PET, and PEEK. One or more of these polymers can be provided as a block copolymer with one or more other polymers, as will be understood by those skilled in the art. Another example of a thermally activated SMP material is polynorbornene, which may or may not be provided in the form of an organic-inorganic hybrid polymer in which some of the polynorbornene units are replaced by polyhedral oligomeric silsesquioxanes (POSS).

[0041] In addition to heat-activated SMPs, the SMP component may alternatively be a light-activated SMP. In this case, the shape of the SMP is deformed in response to irradiation with light of a first wavelength (e.g., UV light). The SMP then returns to its original shape in response to irradiation with light of a different second wavelength. Examples of light-activated SMP materials include, but are not limited to, cinnamic acid and cinnamylidene acetic acid, and more generally, polymers containing cinnamic groups.

[0042] In another example, the SMP component may be an electroactivated SMP, where the shape of the SMP will be deformed in response to the application of a voltage (electric field) of appropriate magnitude. Electroactivated SMPs can be made conductive by including conductive fillers within the polymer material, such as carbon nanotubes (CNTs), carbon fiber, carbon black, or metal (e.g., nickel, Ni) powder.

[0043] In another example, the SMP component may be a magnetically activated SMP, in which case the shape of the SMP will be deformed in response to the application of a magnetic field. Magnetically activated SMPs can be made magnetically responsive by including magnetic fillers within the polymer material, such as magnetite or certain metal (e.g., Ni) particles or fibers.

[0044] SMAs can be deformed while in a cool (unheated) state and then restored to their original shape by the application of thermal energy. Like other shape memory materials, this cycle is reversible. Typically, SMA components are configured to be compliant or spring-like, such as by being formed as thin wires. Examples of SMA materials include, but are not limited to, nickel-based alloys (e.g., Ni—Ti, Ni—Ti—Hf, Ni—Ti—Pd, Ni—Fe—Ga, Ni—Mn—Ga, Ni—Mn—Ga-X (where X=Cu, Co, or Fe)), copper-based alloys (e.g., Cu—Al—Ni, Cu—Al—Ni-Hf, Cu—Sn, Cu—Zn, Cu—Zn-X (where X=Al, Si, or Sn), Cu—Al-Be-X (where X=Zr, B, Cr, or Gd)), iron-based alloys (e.g., Fe—Mn—Si, Fe—Pt, Fe—Pd), silver-based alloys (Ag—Cd), gold-based alloys (Au—Cd), cobalt-based alloys (Co—Ni—Al, Co—Ni—Ga), manganese-based alloys (Mn—Cu), and titanium-based alloys (Ti—Nb). Depending on the alloy composition, some of these SMAs may additionally be magnetic SMAs (MSMAs), also known as ferromagnetic SMAs (FSMAs), which can change shape in response to the application of a magnetic field as an alternative to heat. Examples of MSMA materials include, but are not limited to, the Ni-Mn-Ga based alloys mentioned above, Ni-Fe-Ga, and Fe-Pd.

[0045] In a typical (but not exclusive) embodiment, the capillary array holder 120 is sized as a miniaturized chip. In this context, "miniaturized" is taken to mean that the dimensions (length, width, and height) of the capillary array holder 120 are on the order (or scale) of millimeters (mm), i.e., typically in the range of only 1 mm to 1000 mm (1 meter (m)). In one example, the axial length of the capillary array holder 120 is in the range of 30 mm to 130 mm.

[0046] Generally, any technique appropriate for the materials (e.g., organic polymers, metals, metalloids, etc.) and component sizes utilized can be used to fabricate / manufacture the capillary array holder 120. The particular fabrication technique implemented must be highly suitable for forming the flexible section 136 according to the configurations described herein. Generally, various techniques for fabricating miniaturized articles, including techniques utilized in the fields of microfluidics or microelectronics, may be suitable for fabricating the capillary array device 100. For polymers or plastics, example fabrication techniques include, but are not limited to, microinjection molding and 3D printing. For metals or metalloids, various additive, subtractive, and formative fabrication techniques can be used. Example additive techniques include, but are not limited to, 3D printing (e.g., lithography-based metal fabrication (LMM)), galvanoforming (electroplating), electroforming or electrodeposition, chemical vapor deposition (CVD), and physical vapor deposition (PVD). Examples of subtractive techniques include, but are not limited to, dry etching (e.g., plasma-based etching, including reactive ion etching (RIE) and deep reactive ion etching (DRIE)), wet etching (i.e., chemical etching, such as by using hydrofluoric acid or other acids), as well as subsequent diffusion bonding, micromachining, micromilling, microlaser machining, and micro-electrical discharge machining (EDM). Examples of forming techniques include, but are not limited to, microstamping, microembossing, and LIGA (German: Lithographie, Galvanoformung, Abformung).

[0047] In a typical (but not exclusive) embodiment, the capillaries 124 are made of an optically transparent material. In the context of the present disclosure, an "optically transparent" material is one that allows the transmission of light propagating at wavelengths within a range that includes (at least) the wavelength(s) of the excitation light EX and emitted light EM (described further below and see FIG. 1F) used in the use of the capillary array device 100. Depending on the embodiment, the excitation light EX and / or emitted light EM may be ultraviolet, visible, or infrared light. Examples of materials for the capillaries 124 include, but are not limited to, silica, fused silica, fused quartz, doped (synthetic) fused silica, and polymers such as polytetrafluoroethylene (PTFE) (e.g., for UV detection). A portion (e.g., most) of the length of each capillary 124 may be coated, i.e., circumferentially surrounded, by a coating. The coating may also serve to protect the capillaries 124 from damage or breakage and to block the transmission of light into and out of the capillaries 124. Examples of coating materials include, but are not limited to, polyimide (PI), acrylate, silicone, and fluoropolymer. When coated, at least one section of each capillary 124 is exposed (uncoated), such that the bare (or exposed or uncoated) section, referred to as the "capillary window," is exposed to the environment and thus allows the transmission of light into and out of the capillary 124. The capillaries 124 may be fabricated by any suitable technique now known or later developed. As an example, the capillary 124 may be fabricated by first forming a tubing portion (including the lumen), then coating the entire length of the capillary 124, and then removing (stripping) the coating from a section of the capillary 124 to form the capillary window.

[0048] In the context of the present disclosure, excitation light EX may refer to a beam (or ray) of light directed from a light source external to the capillary array device 100 toward the plurality of capillaries 124 (or toward windows of the plurality of capillaries 124, if provided) to illuminate the sample present within each capillary 124. The beam of excitation light EX may or may not be coherent, depending on the embodiment. Such a light source may be part of an analytical instrument configured to perform optical-based measurements on analytes within the sample, such as to determine properties or characteristics (e.g., the concentration of one or more analytes) and / or to acquire microscopic images, as will be understood by those skilled in the art. Emitted light EM may refer to light emitted from each capillary 124 (or its window) in response to incident excitation light EX, which may be collected (or captured) by a detector (or camera) of the analytical instrument. In some embodiments, emitted light EM may result from different types of stimuli, such as chemical reagents (in which case excitation light EX may not be required).

[0049] In some examples, the excitation light EX may be used to illuminate the sample in the capillary 124 to measure absorbance (or transmittance) and / or acquire a microscopic image. In other examples, the excitation light EX of a selected wavelength may be used to "excite" a target analyte in the sample in the capillary 124 by inducing fluorescence (e.g., from an intrinsically fluorescent analyte, or from a fluorophore (fluorescent dye molecule) added or attached to the analyte, etc.) or similarly phosphorescence. For convenience, the term "excitation" may be used herein to refer to all such cases, including illumination without fluorescence or phosphorescence. In examples of acquiring an image, the emitted light EM is light emitted from the capillary 124 within the camera's field of view, which is processed as needed to construct an image of the sample in the capillary illuminated by the excitation light EX. In examples of measuring absorbance (or transmittance), the emitted light EM emitted from the capillary 124 is attenuated due to partial absorbance of the excitation light EX by the sample in the capillary 124. In such cases, the emitted light EM may be of the same wavelength as the excitation light EX, but may have a lower intensity. In the example of measuring fluorescence, the emitted light EM is light emitted from the analyte in response to the wavelength of the excitation light EX. In such cases, the emitted light EM is of a different wavelength than the excitation light EX. Another example is fluorescence microscopy, where the captured image is based in part on fluorescent emission. For simplicity, the term "emission" is used herein to refer to all such cases, including transmission of non-fluorescent light.

[0050] In a typical (but not exclusive) example, the axial length of the capillary 124 is on the order of millimeters (as defined above), and the outer diameter of the capillary 124 is on the order of micrometers (μm), i.e., typically only 1 μm to 1000 μm (1 mm). In one example, the length of the capillary 124 is in the range of 20 mm to 120 mm. In one example, the outer diameter of the capillary 124 is 80 μm to 200 μm (e.g., hollow fused silica tubing without a protective jacket) or 150 μm to 900 μm (e.g., fused silica core with a protective jacket), with one particular example being 80 μm. Multiple capillaries 124 are typically uniformly spaced apart and positioned side by side along the horizontal axis. In one example, the spacing between adjacent capillaries 124 along the horizontal axis is in the range of 1 mm to 10 mm. In another example, multiple capillaries 124 can be spaced apart for more compact packaging, but crosstalk effects can cause problems with increased background and ghost peaks. Concepts for mitigating these adverse effects while enabling more compact packaging are described in International Application No. PCT / US2021 / 044806, entitled "CAPILLARY ARRAY WINDOW HOLDER AND RELATED SYSTEMS AND METHODS," filed August 5, 2021, the entire contents of which are incorporated herein by reference. In examples where the capillaries 124 include capillary windows, the axial length of the capillary windows is in the range of 500 μm to 4 mm (4000 μm).

[0051] 1A , the capillary array holder 120 includes a stationary section 128, a movable section 132, and a flexible section (or flexible joint) 136 sandwiched between the stationary section 128 and the movable section 132 relative to the device axis. The multiple capillaries 124 can be configured as multiple detection cells to accommodate samples to be detected / measured by an associated analytical instrument. In some embodiments, the sample flows through the capillaries 124 in a direction along the device axis during the optical detection / measurement step, in which case the multiple capillaries 124 serve as multiple flow cells. For these purposes, the capillary array holder 120 can include a detection area 140 that extends through the height (thickness) of the capillary array holder 120, i.e., extending from an upper surface 144 to a lower surface 148 ( FIG. 1D ) of the capillary array holder 120. The detection area 140 is configured to allow transmission of emitted light EM out of the detection area 140, or additionally to allow transmission of excitation light into the detection area 140 (see FIG. 1F ). If the capillaries 124 are coated and provided with windows as described above, the capillaries 124 are attached to the capillary array holder 120 so that the detection area 140 spans the length (at least most of) of the overlying window. In some embodiments, the detection area 140 is part of the stationary section 128, which can facilitate (help) ensuring optical alignment of the detection area 140 with the optical system of the analytical instrument. Alternatively, the detection area 140 may be part of the movable section 132.

[0052] The capillary array device 100 can be mounted in any suitable analytical instrument configured to perform optical-based measurements on analytes contained within a plurality of capillaries 124. Depending on the embodiment, the capillary array device 100 can be mounted directly within the housing or console of the analytical instrument and positioned side-by-side (aligned) with the optical system of the analytical instrument, or can be configured as part of an assembly or cassette that is mounted to the housing or console. For example, the capillary array holder 120 can include one or more mounting features configured to engage a device support, which in turn is configured to engage a receptacle of the analytical instrument such that the capillaries 124 are properly optically aligned with the optical system of the analytical instrument, among other things.

[0053] In some embodiments, the capillary array device 100 integrally includes multiple receptacles. Depending on the embodiment, some receptacles may serve as sources of liquid and / or gel to be loaded (introduced or injected) into the capillaries 124, while other receptacles may serve as receptacles for receiving liquid and / or gel from the capillaries. For example, the liquid may be a sample-containing solution, a buffer solution, a reagent, a liquid containing a label (e.g., a dye, a fluorophore, etc.), or the gel may be a separation medium formed for electrophoresis or chromatography. The multiple receptacles may be formed in the upper surface 144 of the capillary array holder 120 (i.e., the upper surface of the stationary area 128 and / or the movable area 132). Examples of receptacles include wells and recesses (grooves).

[0054] In the illustrated example, the movable area 132 includes a linear (one-dimensional) array of wells 148 arranged (spaced along the horizontal axis) such that each capillary 124 is aligned with a respective one of the wells 148 along the device axis. The movable area 132 also includes a first recess 152 extending along the horizontal axis. Additionally, the stationary area 128 includes a second recess 156 extending along the horizontal axis. The first recess 152 and the second recess 156 have widths greater than the transverse distance spanned by the array of capillaries 124. In this manner, the first recess 152 and the second recess 156 are sufficiently wide along the horizontal axis to simultaneously accommodate all of the capillaries 124. The multiple wells 148 are useful for containing individual samples or other liquids where mixing or cross-contamination is undesirable, thereby facilitating separate analysis of the samples in the corresponding capillaries 124. Movement of liquid or gel between adjacent wells 148 is limited (and preferably prevented entirely) due to the dedicated capillary / groove / well geometry (i.e., well-separated flow paths) and due to surface tension, especially in small or compact configurations where surface tension can play a large role in the fluid dynamics of the capillary array device 100. Recesses 152 and 156 are useful for supplying the same liquid or gel to all capillaries 124 or for receiving the outputs of all capillaries 124 when such outputs do not need to remain separate from one another.

[0055] In the illustrated example, the plurality of capillaries 124 are movable in and out of each well 148 in response to movement of the movable area 132 (movement to the left, from the perspective of FIG. 1A ). The plurality of capillaries 124 are further movable in and out of the first recess 152 in response to further movement of the movable area 132 (further movement to the left). More specifically, each capillary 124 has a first capillary end 160 and an axially opposite second capillary end 164. The plurality of first capillary ends 160 are movable in and out of each well 148 and first recess 152 in response to further movement of the movable area 132 (further movement to the left). In this example, the well 148 is positioned closer to the capillary 124 than the first recess 152. Thus, as the movable area 132 moves toward the capillary 124 (to the left), the first capillary end 160 will first access the well 148 before accessing the first recess 152. Also in this example, the second recess 156 is positioned relative to the fixed position of the capillary 124 such that the second capillary end 164 is permanently positioned within the second recess 156.

[0056] In other embodiments, the second recess 156 may be located in a movable area of the capillary array holder 120 that may be present in addition to the illustrated movable area 132. In other embodiments, the movable area 132 (and / or one or more additional movable areas) may include additional wells and / or recesses depending on the application.

[0057] In this example, FIG. 1A shows the capillary array device 100 in a first (or initial) position. In the first position, the movable section 132 is not moved (e.g., actuated), and therefore the flexible section 136 is relaxed (unflexed). The first position may also correspond to a stored position, i.e., a state in which the capillary array device 100 is stored or initially provided to a user before use. The first position may also correspond to a capillary filling position, i.e., a liquid or gel can be dispensed into the second recesses 156. The liquid or gel is then filled into the plurality of capillaries 124 via the plurality of second capillary ends 164. In this example, the liquid or gel can be passively filled into the plurality of capillaries 124 by capillary action (or wicking), as will be understood by those skilled in the art. Depending on the amount dispensed into the second recesses 156 and the time period allowed for filling, the lumens (internal bores) of the plurality of capillaries 124 can be partially or completely filled with liquid or gel in this manner. Thus, the capillary array device 100 does not require an active fluid movement device (e.g., a positive displacement pump such as a syringe, or a vacuum pump) to fill the plurality of capillaries 124 with liquid or gel. However, in some applications, filling with a particular liquid or gel can be performed electrokinetically, as described below.

[0058] FIG. 1B shows the capillary array device 100 in a second position. The capillary array device 100 is moved from the first position to the second position by moving (e.g., actuating) the movable section 132, as indicated by the leftward arrow in FIG. 1B. The movement of the movable section 132 causes the flexible section 136 to deflect. By way of example, FIG. 1B schematically depicts deflection of the flexible section 136 as involving axial compression of the flexible section 136 (or squeezing of the flexible section 136 between the stationary section 128 and the movable section 132) and outward extension or bulging of the flexible section 136 in either direction along the lateral axis, as indicated in part by the upward and downward arrows in FIG. 1B. Various portions or structural members of the flexible section 128 may move in various directions as part of the deflection response, in which case the outward lateral direction shown in FIG. 1B may be the primary direction of deflection or movement. Flexing of the flexible section 136 changes the overall axial length of the capillary array holder 120, and therefore also changes the overall axial length of the capillary array device 100. In this example, flexing of the flexible section 136 reduces the overall axial length of the capillary array holder 120.

[0059] In the second position, the movable area 132 has been moved (translated linearly along the device axis) far enough (to the left in FIG. 1B ) that the plurality of first capillary ends 160 are now positioned within the corresponding plurality of wells 148. The distance of movement required for the first capillary ends 160 to reach the wells 148 can vary depending on the embodiment. By way of non-limiting example, this distance can be tens or tens of millimeters, or just a few millimeters (e.g., 2-5 mm). In the second position, any liquid or gel contained within the plurality of wells 148 can be passively filled into the plurality of capillaries 124 by capillary action through the plurality of first capillary ends 160. The liquid or gel may be dispensed into the plurality of wells 148 prior to moving the plurality of first capillary ends 160 into the plurality of wells 148, in which case the liquid or gel will be drawn into the plurality of capillaries 124 upon moving the plurality of first capillary ends 160 into the plurality of wells 148. Alternatively, the liquid or gel may be dispensed into the plurality of wells 148 after moving the plurality of first capillary ends 160 into the plurality of wells 148, in which case the liquid or gel will be drawn into the plurality of capillaries 124 upon dispensing the liquid or gel into the plurality of wells 148. Depending on the application, in the second position, the second recess 156 may act as a receptacle to collect any liquid or gel that exits the plurality of second capillary ends 164.

[0060] 1C shows the capillary array device 100 in a third position. The capillary array device 100 has been moved from the second position to the third position by further moving (e.g., actuating) the movable section 132, as indicated by the leftward arrow in FIG. 1C. That is, the movable section 132 has been translated further linearly along the device axis, which in this example means further to the left compared to FIG. 1B. This further movement causes further deflection of the flexible section 136, as partially indicated by the upward and downward arrows in FIG. 1C, and further shortening of the overall axial length of the capillary array holder 120. In the third position, the movable section 132 has been moved far enough (beyond the multiple wells 148) that the multiple first capillary ends 160 are now positioned within the first recesses 152. Similar to the second position, if the first recess 152 contains a liquid or gel, the liquid or gel can then passively fill into the plurality of capillaries 124 by capillary action through the plurality of first capillary ends 160. Alternatively, depending on the application, in the third position, the first recess 152 can act as a receptacle to collect any liquid or gel that exits the plurality of first capillary ends 160.

[0061] 1A-1C schematically depict the state of the flexible region 136 in the first, second, and third positions, respectively. The exact type of reaction of the flexible region 136 to movement of the moveable region 132 depends on the particular configuration of the flexible region 136. As described above and further below, many different configurations for the flexible region 136 are possible and are encompassed by the present disclosure. In FIGS. 1A-1C, the lines depicting the boundaries of the flexible region 136 do not necessarily represent continuous or solid walls or edges. Instead, depending on the flexible configuration, these lines may represent the perimeter of the three-dimensional space occupied by the flexible region 136 in the first, second, and third positions.

[0062] In some examples, all or a portion of the flexible section 136 is configured as a compliant spring that exerts a biasing force toward the movable section 132, i.e., in an axial direction opposite to the axial direction along which the movable section 132 translates from the first position to the second and third positions (biasing to the right in FIGS. 1A-1C ). Thus, the flexible section 136 can bias the capillary array device 100 to the first position shown in FIG. 1A without any force applied to the movable section 132. In this case, when it is desired to move the movable section 132 to the second position shown in FIG. 1B or the third position shown in FIG. 1C , the force applied to the movable section 132 will be large enough to overcome the biasing force of the flexible section 136. When the second or third position is no longer needed, the force applied to the movable section 132 can be released. As a result, the biasing force returns the movable section 132 to the first position (ie, the nominal or initial (default) position) without having to actively push or pull the movable section 132 to the first position.

[0063] The particular use and sequence of movements (movements) of the capillary array device 100 will depend on the particular application for which the capillary array device 100 is being utilized. During one or more time periods during use of the capillary array device 100, one or more of the first, second, and third positions may be utilized one or more times. Also, during one or more time periods during use of the capillary array device 100, optical measurements of samples within the plurality of capillaries 124 may be performed by a suitable analytical instrument to which the capillary array device 100 is attached or installed, as will be understood by those skilled in the art. Such measurements may involve the transmission of light from, or both to, and from, the detection area 140 in which the capillary array holder 120 is located.

[0064] In general, liquid or gel can be dispensed (supplied or delivered) into the plurality of wells 148, first recesses 152, and second recesses 156 by any suitable technique, which can be manual or automated. For example, a user can manually dispense liquid or gel by using an appropriate dispensing device, such as a pipette, syringe, or the like. As another example, the capillary array device 100 can be mounted on an instrument having an automated liquid / gel handling system, as will be understood by those skilled in the art. In such a system, a reservoir (e.g., a bottle) containing a source of liquid or gel can be coupled to a liquid / gel line, and the liquid / gel line can be coupled to one or more pumps and dispensers, which can be movable in an automated manner, such as a motorized pipette head. However, the ability to manually supply liquid and gel to the capillary array device 100 can be considered advantageous in many applications because it avoids the need for an automated liquid / gel handling system.

[0065] The capillary array device 100 may be provided as a "consumable" product, e.g., as a single-use device. That is, the capillary array device 100 may be disposable after use. For example, the capillary array device 100 may be utilized to load samples into a plurality of capillaries 124 once and then perform a single analytical run on those samples. In other words, the capillary array device 100 may be utilized for a single repetition of the capillary loading and analytical run steps. The capillary array device 100 may then be discarded, and a new (fresh) capillary array device 100 may be utilized for additional analytical runs on additional samples. The consumable aspect, or disposability, of the capillary array device 100 eliminates the requirement for cleaning, rinsing, washing, or purging the capillary array device 100 and eliminates any risk of cross-contamination of the capillary array device 100 between separate analytical runs.

[0066] 1D is a longitudinal side view (along the device axis) of capillary array device 100 shown coupled to actuator (assembly) 168 according to one embodiment. Actuator 168 may include an actuator (or actuating device) 172 (or stimulator or activator) of a known type, such as a stepper motor, solenoid, etc., and a mechanical linkage 176 (e.g., an actuator arm, plunger, etc.) coupled to actuator 172. Actuator 172 is configured to linearly translate mechanical linkage 176 along the device axis, as indicated by the double-headed arrow in FIG. 1D . Moveable section 132 may include one or more features configured to be coupled to, engaged with, or at least in contact with actuator 168 (or, more specifically, mechanical linkage 176). In the illustrated example, the movable section 132 includes (e.g., on its underside) or is mounted or attached to a stage or platform 180 configured to be coupled to or in contact with the mechanical linkage 176. In another example, an axial end surface 184 of the movable section 132 is configured to be coupled to or in contact with the mechanical linkage 176. Any suitable coupling mechanism can be provided to create a mechanical coupling between the movable section 132 and the mechanical linkage 176, as will be understood by one of ordinary skill in the art. Examples of coupling mechanisms include, but are not limited to, snap-fit mechanisms (e.g., the mechanical link 176 fits into a recess in the movable section 132), abutment mechanisms (e.g., the surfaces of the movable section 132 and the mechanical link 176 engage, allowing the mechanical link 176 to push the movable section 132 toward the flexible section 136, or, if the flexible section 136 is not spring-loaded, additionally pull the movable section 132 away from the flexible section 136), fastening mechanisms (e.g., using fastening components such as clamps, spring clips, threads, etc.), and magnetic coupling mechanisms (e.g., the movable section 132 and the mechanical link 176 include magnets oriented to attract each other).

[0067] In another example, the movable section 132 and the mechanical linkage 176 may be coupled in a contactless manner. For example, the movable section 132 and the mechanical linkage 176 (or the actuator 172 itself without the mechanical linkage 176) may include magnets oriented to repel each other, such that movement of the mechanical linkage 176 toward the movable section 132 moves the movable section 132 away from the flexible section 136. In this context, a "magnet" may be a permanent magnet or an electromagnet. If at least one of the magnets (in the movable section 132, or the mechanical linkage 176, or the actuator 172) is an electromagnet, the magnetic field may be controlled by a current supplied to the electromagnet. In this case, the mechanical linkage 176 may not be needed, or at least the mechanical linkage 176 may not be needed to move toward and away from the movable section 132.

[0068] In another example, actuation may be performed manually by a user, in which case one or more of elements 172, 176, and 180 in Figure ID may represent levers, handles, or other components operated by the user.

[0069] In the example described above in connection with FIG. 1D , actuator 168 may be referred to as an extrinsic actuator to distinguish it from the internal actuators described earlier in this disclosure. External actuators often rely on physical (or mechanical) contact between an actuation device (or stimulator or activation device) 172 and the movable section 132, and thus cooperate with some type of mechanical linkage 176 as described earlier. Thus, external actuators are often “contact” actuators, with at least one exception being the example above utilizing repelling magnets. In other examples, actuator 168 may be an internal actuator, in which at least a portion of movable section 132 and / or flexible section 136 are considered to include internally actuated components as described earlier in this disclosure. When the actuator 168 is configured as an internal actuator, the actuation device (or stimulator or activator) 172 can be a voltage source (e.g., as part of an electrical circuit), a heat source (e.g., a resistive-type heating device that generates Joule (Ohmic) heating), a light source (e.g., a lamp, light-emitting diode (LED), laser, laser diode (LD), etc. configured to emit electromagnetic energy at an appropriate wavelength), or a magnetic source (e.g., one or more magnets). If an internal actuator is provided, the connection (or coupling) between the actuation device 172 and the internal actuator can be either an electrical interconnection (wiring and electrodes), or a "contactless" (or wireless) connection, such as thermal or electromagnetic energy (e.g., a light beam) propagating through air, or a magnetic field.

[0070] 1E is a longitudinal side view of a capillary array device 100 shown coupled to an electrical circuit according to one embodiment. In particular, the capillary array device 100 is coupled to a high voltage (HV) source 188. In this example, the capillary array device 100 includes a plurality of electrodes 192 disposed in one or more of the wells 148, the first recess 152, and the second recess 156. The electrodes 192 may be disposed in electrical communication with the HV source 188 (and any associated electrical circuitry) by suitable electrical interconnections, such as electrical wiring; electrical contacts; fluid-tight electrical feedthroughs or "vias" formed through the body of the capillary array holder 120 beneath or alongside the wells 148, the first recess 152, and / or the second recess 156, etc., as will be understood by those skilled in the art. The electrodes 192 may be provided and electrically coupled to the HV source 188 as needed for a given application. In particular, the electrical configuration can be used to apply a voltage (potential difference) across the length of the capillaries 124 (between the first and second axial ends 160 and 164). For example, the electrode 192 located within the well 148 and / or the first recess 152 can serve as an anode, and the electrode 192 located within the second recess 156 can serve as a cathode. The applied voltage can be used to assist in filling the plurality of capillaries 124 with liquid and / or to transport liquid through the plurality of capillaries 124 by electrokinetic forces. In some examples, the applied voltage is used as part of performing electrophoresis (particularly capillary electrophoresis or CE) on samples within the plurality of capillaries 124, as described elsewhere herein. As one example, the applied voltage can be in the range of 0.2 kV to 5 kV.

[0071] In one example, one or more electrodes 192 may also be utilized to generate an electric field that stimulates (activates) an electrically activated internal actuator as described above.

[0072] 1E embodiment, the plurality of wells 148 need not be similarly coupled to the HV source 188; instead, the plurality of wells 148 may be individually addressable by the HV source 188. For example, a suitable switch 196 may be provided in an electrical circuit between the HV source 188 and each of the plurality of electrodes 192 in a corresponding plurality of wells 148. With this configuration, a voltage may be selectively applied to any one or more of the plurality of capillaries 124, and may be applied according to a predetermined sequence if dictated by the method protocol. Furthermore, a voltage may be applied one or more times to one or more selected capillaries 124 according to predetermined pulse width(s), pulse shape(s), and sequence of pulses.

[0073] 1F is a longitudinal side view of a capillary array device 100 shown coupled to an optical-based measurement device (or system) 106 according to an embodiment of the present disclosure. The optical-based measurement device 106 may be configured and function according to any now known or later developed technique suitable for analyzing samples within the plurality of capillaries 124. In a typical example, the optical-based measurement device 106 includes a light source 110 and a photodetector (or camera) 114. The light source 110 (and any associated excitation optics required) is configured to generate and direct an excitation light beam EX toward portions of the plurality of capillaries 124 (which may be the plurality of capillary windows as described above) positioned in a detection area 160. The photodetector or camera 114 (and any associated emission optics required) is configured to receive or capture an emission light beam EM emitted from the portions of the plurality of capillaries 124 located in the detection area 160. As illustrated, both sample excitation and detection can be performed on the same side of the capillary array device 100, such as the top side as illustrated. Alternatively, the optical-based measurement device 106 can be configured for trans-illumination, where sample excitation and detection are performed on opposite sides (or both sides) of the capillary array device 100 (e.g., the light source 110 can be positioned above the capillary array device 100 and the photodetector or camera 114 can be positioned below the capillary array device 100, or vice versa). If necessary, an appropriately configured light trap (or "beam dump") 118 can be positioned to capture or absorb stray excitation and / or emission light. In some applications, sample excitation or stimulation can be performed by means other than a light beam, such as by a chemical reaction, in which case the light source 110 can be omitted, or at least not utilized in such applications.

[0074] In one embodiment, the capillary array device 100 is configured for capillary electrophoresis (CE), i.e., to perform a CE run on samples in the multiple capillaries 124. In this case, and in the example illustrated in Figures 1A-1F, the multiple wells 148 can be utilized as multiple sample wells configured to accommodate individual samples (e.g., volumes of sample solution) for which analytical separation by CE is desired. The first recess 152 can be utilized as a buffer recess configured to accommodate an appropriate buffer solution. The buffer solution can be configured to function as an electrolyte capable of conducting electric charge (i.e., as an ion source) and perform other functions, such as pH control. The second recess 156 can be utilized as a gel recess configured to accommodate a CE separation medium, which is typically provided in the form of a polymer gel that may be solid but porous. The specific type and composition of the CE separation medium will depend on the type of analyte to be separated, as will be understood by those skilled in the art. Examples of CE separation media include, but are not limited to, polyacrylamide, agarose, and certain starches.

[0075] A method for analyzing a sample by CE will now be described. The method utilizes a capillary array device configured for CE and according to any of the embodiments or examples described herein, such as the capillary array device 100 described above and illustrated in FIGS. 1A-1F. According to the method, the capillary array device 100 is initially provided in a first position, shown in FIG. 1A, which may be referred to as a gel-filling position. The second recesses 156 (gel recesses) are filled with a desired amount of CE separation medium. The amount of CE separation medium dispensed into the second recesses 156 may depend on the particular method protocol being implemented, which may depend on the number and length of the capillaries 124 and whether the plurality of capillaries 124 is fully or partially filled. Next, with the plurality of second capillary ends 164 already disposed within the second recesses 156, the CE separation medium is passively filled (or drawn) into the plurality of capillaries 124 by capillary action. Before or after filling the CE separation medium into the plurality of capillaries 124, the plurality of wells 148 (sample wells) are filled with individual samples (which may be the same or different in composition from one another) and the first recess 152 (buffer recess) is filled with a buffer solution.

[0076] Next, the capillary array device 100 is moved to a second position shown in FIG. 1B, which may be referred to as a sample injection position. Specifically, the movable section 132 is actuated to move toward the flexible section 136 relative to the (stationary) plurality of capillaries 124 and the stationary section 128 until the plurality of first capillary ends 160 enter the plurality of wells 148. With the plurality of first capillary ends 160 now positioned within the plurality of wells 148, sample is then loaded into the plurality of capillaries 124. In the second position, an electrical circuit is completed between the HV source 188 ( FIG. 1E ) and the plurality of electrodes 192 of the plurality of wells 148 and second recesses 156 due to the electrolytic properties of the liquid and gel within the plurality of capillaries 124, the plurality of wells 148, and the second recesses 156. Thus, a voltage may now be applied across the length of the plurality of capillaries 124. In particular, a voltage pulse may be applied to electrokinetically inject the sample so that it enters the front region of the plurality of capillaries 124. In some instances, this electrokinetic assistance may be required due to the flow resistance presented by the gel-phase CE separation medium present within the plurality of capillaries 124.

[0077] Next, the capillary array device 100 is moved to a third position shown in FIG. 1C , which may be referred to as a CE run position. Specifically, the movable section 132 is actuated to move further toward the flexible section 136 relative to the (stationary) plurality of capillaries 124 and the stationary section 128. During this movement, the plurality of first capillary ends 160 pass through the plurality of wells 148 and enter the first recesses 152. In the third position, an electrical circuit is completed between the HV source 188 ( FIG. 1E ) and the plurality of electrodes 192 in the first recesses 152 and second recesses 156 due to the electrolytic properties of the liquid and gel within the plurality of capillaries 124, the first recesses 152, and the second recesses 156. A voltage is then applied to the plurality of capillaries 124 according to predetermined operating parameters (e.g., magnitude (constant and / or varying or ramping); overall time duration of the applied voltage; pulse width, pulse shape (e.g., square, triangular, sinusoidal, etc.), and pulse sequence (including pulse frequency)) suitable for inducing electrophoretic separation of the different analytes of the sample within each capillary 124 in a manner understood by one of ordinary skill in the art. Briefly, within each capillary 124, the different analytes of the sample migrate under the influence of the applied voltage through the CE separation medium at different speeds and thereby become separated from one another along the length of the capillary 124. The separated analytes within each capillary 124 can then be detected / measured at the detection area 140 by the optical-based measurement device 106 ( FIG. 1F ). Thereafter, after acquiring CE data from the sample, the capillary array device 100 can be discarded in some embodiments, as described above.

[0078] The present disclosure also encompasses a sample analysis system (or device, analytical instrument, etc.) including an actuator and / or HV source (and associated electrical circuitry) and / or optical-based measurement device, such as actuator 168, HV source 188, and optical-based measurement device 106, described above and illustrated in FIGS. 1D, 1E, and 1F, respectively. In one embodiment, actuator 168, HV source 188, and optical-based measurement device 106 may be integrated into a housing or console of the sample analysis system. The sample analysis system may or may not be portable. Indeed, capillary array device 100 may be attached to or installed in the sample analysis system. Depending on the application or embodiment, this installation may involve one or more of: mounting the stationary section 128 in a fixed position such that the capillary array device 100 (particularly the detection area 140) is properly aligned with the optical elements of the optical-based measurement device 106; coupling the electrodes 192 to the HV source 188; and coupling the movable section 132 to the actuator 168. As noted above, in some embodiments, any liquids (including samples) and gels to be utilized may be dispensed into the wells 148 and / or recesses 152 and 156 prior to installing the capillary array device 100 in a sample analysis system. In such cases, no fluidic devices or circuitry (whether provided by the sample analysis system or not) need be coupled to the capillary array device 100.

[0079] 2 is an exploded view of an example of a capillary array device 100 and a device support 200 configured to firmly support the capillary array device 100 during its operation, according to one embodiment. For simplicity, the capillaries 124 are not shown. As one example, the capillary array device 100 can first be attached to the device support 200 externally from a sample analysis system such as those described herein, and then the assembly of the capillary array device 100 and the device support 200 can be installed within the sample analysis system. As another example, the device support 200 can be a fixed component of a receptacle of the sample analysis system that accepts the capillary array device 100, in which case the capillary array device 100 can be attached to the device support 200 during or after loading the capillary array device 100 into the receptacle. In the illustrated example, the body of the device support 200 includes an upper surface 222 in which one or more alignment holes (or mounting holes) 226, which can be either blind holes or through-holes, are formed. The capillary array device 100 includes one or more alignment posts (or pins, etc.) 230 that depend downward from the underside of the resting area 128. The number and positional arrangement (pattern) of the alignment posts 230 match those of the alignment holes 226. The capillary array device 100 is attached to the device support 200 by aligning the alignment posts 230 with the alignment holes 226 and then lowering the capillary array device 100 onto the device support 200 so that the alignment posts 230 extend into the corresponding alignment holes 226. With this configuration, after the capillary array device 100 is attached to the device support 200 and placed in a receptacle of a sample analysis system, the detection area of the capillary array device 100 is properly optically aligned (lined up) with the optical-based measurement device 106 ( FIG. 1F ) of the sample analysis system.

[0080] In another example, the capillary array device 100 can include a plurality of alignment holes 226, and the device support 200 can include a plurality of alignment posts 230. The alignment holes 226 and alignment posts 230 can have any round or polygonal shape. In another example, the alignment holes 226 and alignment posts 230 can extend in at least one dimension (e.g., in the x- or y-direction). For example, the alignment holes 226 can be shaped as slots, and the alignment posts 230 can be shaped as flat plates or tabs.

[0081] In one example, the device support 200 can include an actuator opening 234 formed through a thickness (height) of the device support 200 that is configured to accommodate one or more components of an actuator 168 (FIG. 1D) of a sample analysis system. In one example, the device support 200 and the actuator 168 can be mounted together as an assembly.

[0082] In one example, the device support 200 may include one or more linear guide slots 238 formed in its upper surface 232, and the capillary array device 100 may include one or more linear guide rails 242 depending downward from the underside of the movable section 132. The number and positional arrangement (pattern) of the linear guide rails 242 match those of the linear guide slots 238. Thus, when the capillary array device 100 is mounted on the device support 200, the linear guide rails 242 extend into the corresponding linear guide slots 238. The engagement between the linear guide slots 238 and the linear guide rails 242 may help maintain the linearity of the movement of the movable section 132 along the device axis. Alternatively, the capillary array device 100 may include multiple linear guide slots 238, and the device support 200 may include multiple linear guide rails 242.

[0083] FIG. 3 is a longitudinal side view of another example of a capillary array device 300 according to another embodiment of the present disclosure. FIG. 3 shows the capillary array device 300 in a deflected position (deformed position), corresponding to, for example, the second or third position shown in FIG. 1B and FIG. 1C , respectively. The capillary array device 300 includes a flexible section 336 that is configured differently from the flexible section 136 of the capillary array device 100 described above in connection with FIG. 1A-1C . As depicted schematically in FIG. 3 , in response to axial movement of the movable section 132 (as indicated by the left-pointing arrow in FIG. 3 ) and the resulting axial compression of the flexible section 336, the flexible section 336 is configured to deflect and move primarily in the downward direction (along the elevation axis, away from the overlying plurality of capillaries 124), as indicated by the downward-pointing arrow in FIG. 3 . In one example, and as noted above, flexible section 336 may include one or more hinges (not shown) (e.g., hinges that pivot about the y-axis) that facilitate this type of deflection. The configuration of capillary array device 200 may in many other respects be the same as or similar to that of capillary array device 100, described above and illustrated in Figures 1A-1F.

[0084] 4A-4G illustrate an example of a capillary array device 400 according to another embodiment. FIGS. 4A and 4B are top perspective and top plan views, respectively, of the capillary array device 400. The capillary array device 400 includes a flexible section 436 having an open-frame configuration as generally described above. Specifically, in this example, the flexible section 436 is configured as a series of axially aligned, diamond-shaped elastic (flexible) segments 446. Depending on their relative positions, each elastic segment 446 can be integrally joined to two adjacent elastic segments 446, to an adjacent elastic segment 446 and the stationary section 128, or to an adjacent elastic segment 446 and the movable section 132. The elastic segments 446 are defined by a web of thin structural members (or compliant beams) 450 (as described above), which define diamond-shaped openings 454 ( FIG. 4B ). The elastic segments 446, and consequently the flexible region 436 as a whole, act as a compliant spring that responds to movement of the moveable region 132 in the manner previously described in this disclosure. Movement of the moveable region 132 compresses the elastic segments 446 axially, causing their diamond shape to "flatten," and the elastic segments 446 may also move outward along the lateral axis.

[0085] In this example, the capillary array device 400 also includes one or more structural braces 458 configured to stabilize the linear translation of the movable section 132 and / or contribute to the compliance and spring action of the flexible section 436. The braces 458 may or may not be considered part of the flexible section 436, depending on the example. For example, the braces 458 may be considered thin structural members of the flexible section 436. In the illustrated example, the capillary array device 400 includes at least two braces 458, one on each side of the elastic segment 446 relative to the horizontal axis. Each brace 458 is attached to or integral with the stationary section 128 at one end and attached to or integral with the movable section 132 at the other end. In the illustrated example, the brace 458 is shaped as a strap that may have a larger dimension at its end where it joins the static section 128 and the movable section 132 to improve the robustness of the configuration. The brace 458 may have a curved shape, as illustrated. In this example, in response to movement of the movable section 132 toward the flexible section 436, the brace 458 moves or bulges outward along a lateral axis.

[0086] The configuration of the capillary array device 400 can be the same as or similar to that of the capillary array device 100 described above and illustrated in FIGS. 1A-1C in many other respects. For example, the plurality of capillaries 124 can be secured and arranged in the capillary array holder of the capillary array device 400 in the same or similar manner as the configuration of the capillary array device 100. Thus, the plurality of capillaries 124 can be secured to the stationary section 128 such that the plurality of second capillary ends 164 are permanently disposed in the second recesses 156, and the plurality of first capillary ends 160 can be selectively movable into the plurality of wells 148 and the first recesses 152 in response to movement of the movable section 132. Furthermore, the capillary array device 400 can be utilized in cooperation with components of a sample analysis system, such as those described above in connection with FIGS. 1D-1F.

[0087] In this example, the top surface (or the top surface area between the openings) of the capillary array holder (stationary area 128 and movable area 132) includes a plurality of grooves 462 to which the plurality of capillaries 124 are attached. At least some of the plurality of grooves 462 in the stationary area 128 may serve as fixing points 466 at which the capillaries 124 are fixed to the stationary area 128. As one non-exclusive example, a suitable glue may be applied to the fixing points 466. The plurality of grooves 462 in the movable area 132 may help guide the linear movement of the movable area 132 relative to the plurality of capillaries 124.

[0088] Figure 4C is a cutaway top perspective view of the capillary array device 400 taken along line AA shown in Figure 4B, which corresponds to one of the plurality of capillaries 124 and its associated groove 462. Figure 4D is a cutaway longitudinal side view taken along the same line AA shown in Figure 4B, thus showing the same capillary 124 and associated groove 462. In this example, some of the sections of the groove 462, such as those at the entrance into the well 148 and first recess 152, may include tapered or conical portions 470 to help guide the capillary 124 during movement of the movable section 132 as the capillary 124 enters open spaces such as the well 148 and first recess 152.

[0089] 4E-4G are top plan views of the capillary array device 400 shown in the first, second, and third positions, respectively. For simplicity, the flexible section 436 is not shown in FIGS. 4E-4G. In this example, the capillary array device 400 operates in the first, second, and third positions in the same manner as the capillary array device 100 described above in connection with the first, second, and third positions shown in FIGS. 1A-1C.

[0090] 5A and 5B illustrate an example of a capillary array device 500 according to another embodiment. Specifically, FIG. 5A is a top perspective view of the capillary array device 500, and FIG. 5B is a top plan view of the capillary array device 500. The plurality of capillaries 124 are not shown in FIGS. 5A and 5B. In this example, the capillary array device 500 includes guide features configured to guide the axial movement of the capillary array device 500 into the various operating positions described herein. Such guide features may be integrated with the stationary section 528 and the movable section 532 of the capillary array device 500. Specifically, as illustrated, the movable section 532 includes a first axial leg 574 and a first axial recess (or channel, or other axially extending space) 578, both of which extend along the device axis but on opposite sides of the movable section 532 relative to the lateral axis. The rest section 528 includes a second axial leg 582 and a second axial recess (or channel, or other axially extending space) 586, both of which extend along the device axis but on opposite sides of the rest section 528 relative to the lateral axis. In operation, as the moveable section 532 moves axially toward the flexible section 436, the first axial leg 574 moves axially through or adjacent to the second axial recess 586, and the first axial recess 578 moves axially around or adjacent to the second axial leg 582 (or, in fact, the second axial leg 582 moves axially through or adjacent to the first axial recess 578). With this configuration, these guide features (first axial leg 574, first axial recess 578, second axial leg 582, and second axial recess 586) assist in maintaining the linearity or straightness of the axial movement of the movable section 532 relative to the plurality of capillaries 124 and the stationary section 528, such as by limiting the lateral movement (along the lateral axis) of the movable section 532. To this end, the first axial leg 574 and the second axial leg 582 may or may not contact the surfaces of the second axial recess 586 and the first axial recess 578, respectively, during movement of the movable section 532.

[0091] Also in this example, the first axial leg 574 can include a first shoulder 590, and the second axial leg 582 can include a second shoulder 594. The first shoulder 590 and the second shoulder 594 can act as mechanical stops that limit the axial extent of movement of the movable section 532. In other words, if the movable section 532 moves far enough toward the flexible section 436, the first shoulder 590 will contact a surface of the stationary section 528 and / or the second shoulder 594 will contact a surface of the movable section 532, thereby preventing further axial movement.

[0092] In the illustrated example, the flexible section 436 of the capillary array device 500 is the same as or similar to the flexible section 436 of the capillary array device 400 described above and illustrated in Figures 4A and 4B. However, the flexible section 436 of the capillary array device 500 may have any of the flexible configurations described and / or illustrated herein.

[0093] The configuration of the capillary array device 500 may be the same or similar in many other respects to the capillary array device 100 described above and illustrated in Figures 1A-1C, and / or the capillary array device 400 described above and illustrated in Figures 4A and 4B. For example, the capillary array device 500 may be capable of axial movement between first, second, and third positions, as described above and illustrated in Figures 1A-1C or 4E-4G. Furthermore, the capillary array device 500 may be utilized in cooperation with components of a sample analysis system, such as those described above in connection with Figures 1D-1F.

[0094] 6A and 6B illustrate an example of a capillary array device 600 according to another embodiment. Specifically, FIG. 6A is a top perspective view of the capillary array device 600, and FIG. 6B is a top plan view of the capillary array device 600. In this example, the capillary array device 600 includes two or more movable areas, specifically, a first movable area 632 and a second movable area 603. The capillary array device 600 also includes two or more stationary areas, specifically, a first stationary area 628 and a second stationary area 607 (or equivalently, the stationary areas of the capillary array device 600 include a first stationary portion 628 and a second stationary portion 607). In the device plane, the first rest area 628 is axially disposed between the first movable area 632 and the second movable area 603, and the second rest area 607 surrounds the first movable area 632 and the second movable area 603. In this example, the first rest area 628 and the second rest area 607 are integrally joined, i.e., they have a single-piece construction. However, in other examples, the first rest area 628 and the second rest area 607 may be separate components.

[0095] In this example, the detection area 140 is located in the first stationary area 628. The multiple wells 148 and the first recess 152 are located in the first movable area 632, and the second recess 156 is located in the second movable area 603. In addition, the capillary array device 600 includes a third recess 611 that is located in the first movable area 632, but may alternatively be located in the second movable area 603, depending on the embodiment. The third recess 611 may serve as an additional liquid or gel source. As with the other embodiments, additional recesses may be provided as needed for a particular application. In this example, the first recess 152 is positioned axially closer to the multiple capillaries 124 than the third recess 611 and the multiple wells 148, and the multiple wells 148 are positioned axially farther from the multiple capillaries 124 than the first recess 152 and the third recess 611, and therefore the third recess 611 is positioned axially between the first recess 152 and the multiple capillaries 124.

[0096] In this example, the capillary array device 600 includes a flexible section 636 that includes a plurality of thin structural members (or compliant beams) 650 separated by a plurality of openings 654 that pass through (through) the thickness (height) of the flexible section 636. For example, and as illustrated, one or more structural members 650 interconnect (i.e., are integrally joined or attached to) the second stationary section 607 and one side of the first movable section 632, and one or more additional structural members 650 interconnect ("opposite" relative to the horizontal axis) the second stationary section 607 and the opposite (other) side of the first movable section 632. Similarly, one or more additional structural members 650 interconnect the second stationary area 607 and one side of the second movable area 603, and one or more additional structural members 650 interconnect the second stationary area 607 and the opposite (other) side of the second movable area 603. Stated differently, each structural member 650 is coupled to the second stationary area 607 and also to either the first movable area 632 or the second movable area 603. In this example, the plurality of structural members 650 are joined or attached to an inner wall 615 of the second stationary area 607 (e.g., the wall 615 facing the central device axis) and to an outer wall of the first movable area 632 or the second movable area 603. As further illustrated, each of the plurality of structural members 650 may include one or more "thick" areas or boxes 619, which may be solid or partially hollow. Each box 619 is larger or "thicker" than the rest of (the "thin" area of) its corresponding structural member 650, where the terms "thick" and "thin" are relative to each other. The boxes 619 can be useful in controlling the compliance of the structural members 650. For example, a larger (e.g., longer) box 619 can decrease the compliance. Thus, the compliance of the multiple structural members 650 can be controlled (or adjusted or tuned) by selecting the size of the box 619 (and / or the number of boxes 619) provided in each structural member 650. The boxes 619 can also be useful in providing enhanced structural support for the structural members 650.

[0097] In this example, the flexible section 636 is configured such that axial movement of the first movable section 632 or the second movable section 603, as indicated by the straight double-headed arrow in Figure 6B, will cause the corresponding plurality of structural members 650 to pivot (or swing) within the plane of the device, as indicated by the curved double-headed arrow in Figure 6B. The pivot point is located at the interface between the second stationary section 607 and the first movable section 632 and second movable section 603.

[0098] In this example, the capillary array device 600 is axially movable between at least three positions (first, second, and third). FIGS. 6A and 6B show the capillary array device 600 in a first (or initial, or retracted) position. In the first position, the first movable section 632 and the second movable section 603 are not moved (e.g., actuated), and thus the flexible section 636 is relaxed (not deflected). In the first position, the plurality of first capillary ends 160 are positioned inside the first recesses 152. Therefore, when a liquid or gel is dispensed into the first recesses 152, the liquid or gel passively fills into the plurality of capillaries 124 via the plurality of first capillary ends 160 by capillary action. The capillary array device 600 can then be moved to a second position by axially moving the first movable section 632 toward the first stationary section 628 (translating the first movable section 632 axially to the left in FIG. 6B ). In the second position, the plurality of first capillary ends 160 are now disposed within third recesses 611, which can be filled with a liquid or gel that can be different from the liquid or gel provided in the first recesses 152 before or after movement to the second position. The capillary array device 600 can then be moved to a third position by further axially moving the first movable section 632 toward the first stationary section 628 (translating the first movable section 632 axially to the left in FIG. 6B ) and further axially moving the second movable section 603 toward the first stationary section 628 (translating the second movable section 603 axially to the right in FIG. 6B ). At the third position, the plurality of first capillary ends 160 are now positioned within the plurality of wells 148 that may be filled with a liquid or gel that may be different from the liquid or gel provided in the first recess 152 and the third recess 611, either before or after movement to the third position. In addition, the plurality of second capillary ends 164 are now positioned within the second recesses 156 that may be filled with a liquid or gel that may be different from the liquid or gel provided in the plurality of wells 148, the first recess 152, and the third recess 611, either before or after movement to the third position.

[0099] In another example, the third position can be divided into a third position and a separate fourth position. At the third position, the plurality of first capillary ends 160 are positioned within the plurality of wells 148. At the subsequent fourth position, the plurality of second capillary ends 164 are positioned within the second recesses 156. Alternatively, the plurality of second capillary ends 164 can be positioned within the second recesses 156 at the third position, and then the plurality of first capillary ends 160 can be positioned within the plurality of wells 148.

[0100] The particular use of the capillary array device 600, the sequence of movements (actuations), and the number of different positions will depend on the particular application for which the capillary array device 600 is being utilized. Thus, the sequence of movements may differ from that just described. For example, in the first position, the first capillary ends 160 may initially be positioned in any of the receptacles (e.g., the wells 148, the first recess 152, and the third recess 611) of the first movable area 632, or the first capillary ends 160 may not initially be positioned in any of these receptacles. At other positions (e.g., second, third, fourth and subsequent) reached subsequent to the first position, the plurality of first capillary ends 160 may or may not be positioned in one of the receiving portions of the first movable area 632, and the plurality of second capillary ends 164 may or may not be positioned in one of the receiving portions (e.g., second recesses 156) of the second movable area 603.

[0101] As with other embodiments, multiple electrodes (such as the multiple electrodes 192 described above in connection with FIG. 1E) may be provided in any of the multiple wells 148, the first recess 152, the second recess 156, and the third recess 611 to fill the liquid or gel into the multiple capillaries 124 and / or transport the liquid or gel through the multiple capillaries 124 by electrokinetics.

[0102] In this example, the flexible section 636 is configured as a compliant spring that biases the first movable section 632 and the second movable section 603 toward the first position shown in FIGS. 6A and 6B . That is, the relaxed state of the flexible section 636 corresponds to the first position. In this example, as best seen in FIG. 6B , in the relaxed state, the structural members 650 of the flexible section 636 are oriented at an angle relative to the horizontal axis (and device axis). As the first movable section 632 moves toward the first rest section 628 (left) or the second movable section 603 moves toward the first rest section 628 (right), the structural members 650 will pivot in the associated direction and begin to deflect. This pivoting may cause the structural members 650 to begin to “stretch,” i.e., the angle between the structural members 650 and the horizontal axis may decrease. Depending on the embodiment, this type of deflection may involve some degree of compression and / or stretching and / or bending of the structural members 650. With this configuration, upon removal of the actuation force applied to the first movable section 632 or the second movable section 603, the first movable section 632 or the second movable section 603 will return to the relaxed region (first position) shown in Figures 6A and 6B due to the biasing force provided by the plurality of structural members 650.

[0103] 1D , an actuator may be configured to selectively and independently actuate the movement of the first movable section 632 and the second movable section 603. Alternatively, two such actuators 168 may be provided, where a first actuator is coupled to or in contact with the first movable section 632 and a second actuator is coupled to or in contact with the second movable section 603.

[0104] The configuration of capillary array device 600 may in many other respects be the same as or similar to that of capillary array device 100 described above and illustrated in Figures 1A-1C, and / or capillary array device 400 described above and illustrated in Figures 4A and 4B, and / or capillary array device 500 described above and illustrated in Figures 5A and 5B. Furthermore, capillary array device 600 may be utilized in cooperation with components of a sample analysis system, such as those described above in connection with Figures 1D-1F.

[0105] As with other embodiments, capillary array device 600 can be configured for CE as described herein. In one example, multiple wells 148 are utilized as sample wells, first recess 152 is utilized as a (first) gel recess configured to accommodate a (first) CE separation medium, second recess 156 is utilized as a buffer recess, and third recess 611 is utilized as a (second) gel recess configured to accommodate a (second) CE separation medium having a different composition than the first CE separation medium accommodated in first recess 152.

[0106] A method for analyzing a sample by CE utilizing a capillary array device 600 will now be described. According to this method, the capillary array device 600 is initially provided in a first position, as shown in FIG. 6A , with the ends 160 of the first capillaries located within the first recesses 152 (first gel recesses). The first recesses 152 are filled with a desired amount of a first CE separation medium, and the third recesses 611 (second gel recesses) are filled with a desired amount of a second CE separation medium. The capillary array device 600 is held in the first position for a predetermined period of time sufficient to partially fill the plurality of capillaries 124 with the first CE separation medium. In other words, at the first position, a plug of the first CE separation medium is formed within each capillary 124. After the time period allocated for filling the first CE separation medium has elapsed, the capillary array device 600 is moved to a second position where the ends 160 of the first capillaries are within the third recesses 611. The capillary array device 600 is held at the second position for a predetermined period of time sufficient to partially fill the capillaries 124 with the second CE separation medium, thereby forming plugs of the second CE separation medium in each capillary 124. In this manner, an axially position-dependent composite CE separation matrix is formed in each capillary 124, with each CE separation matrix comprising an axially "stacked" arrangement of plugs of different CE separation media. The use of multiple different CE separation media in the same capillary 124 may provide advantages in the separation and analysis of certain types of samples. Depending on the amount of time the capillary array device 600 is held at the first and second positions, plugs of the first CE separation medium and plugs of the second CE separation medium may be directly adjacent to each other in each capillary 124. Alternatively, the plug of first CE separation medium and the plug of second CE separation medium can be spatially separated from each other, with the intervening space being occupied by a buffer solution and / or a sample solution.

[0107] After the time period allocated for filling the second CE separation medium has elapsed, the capillary array device 600 is moved to a third position where the first capillary ends 160 are positioned within the wells 148 (sample wells) and the second capillary ends 164 are positioned within the second recesses 156 (buffer recesses). Before or after moving to the third position, the wells 148 are filled with sample and the second recesses 156 are filled with buffer solution. At the third position, an electrical circuit is formed between an HV source (e.g., HV source 188 shown in FIG. 1E) and electrodes (e.g., electrodes 192 shown in FIG. 1E) positioned within the wells 148 and the second recesses 156. A voltage pulse is then applied across the length of the capillaries 124 to electrokinetically inject the sample into the front regions (first capillary ends 160) of the capillaries 124 as a sample plug. Another voltage is then applied, as described elsewhere herein, according to predetermined operating parameters effective to induce electrophoretic separation of different analytes of the sample in each capillary 124. The separated analytes in each capillary 124 may then be detected / measured in the detection area 140 by an optical-based measurement device (e.g., optical-based measurement device 106 shown in FIG. 1F). Thereafter, as with other embodiments, after acquiring CE data from the sample, the capillary array device 600 may be discarded, if desired.

[0108] 7A and 7B illustrate one example of a capillary array device 700 including an internal actuator 723. In this example, the internal actuator 723 is a DEA, but may alternatively be configured according to any of the other examples of internal actuators described herein. FIG. 7A is a longitudinal side view of the capillary array device 700 when in an unactuated position, which may correspond to a first position as described herein. FIG. 7B is a longitudinal side view of the capillary array device 700 when in an actuated position, which may correspond to a second position, a third position, a fourth position, etc. as described herein. For simplicity, FIGS. 7A and 7B do not show certain other features that may be included and described herein, such as a plurality of capillaries 124 and a plurality of receptacles (wells, recesses, etc.).

[0109] In this example, the movable area 132 is considered to include an internal actuator 723 and a non-internal actuatable element 727 coupled to or in contact (or contactable with) the internal actuator 723. The non-internal actuatable element 727 may be, for example, a body of material corresponding to the movable area 132 described above in connection with FIGS. 1A-1F , which may include one or more of the housings described herein. Also, in this example, the capillary array device 700 includes an actuator (assembly) 768 configured to actuate (flick) (or stimulate, activate, etc.) the internal actuator 723. In this example, the actuator 768 includes an actuator 772 in the form of a voltage source, two or more electrodes 731 in contact with upper and lower flat sides of the internal actuator 723, and an electrical (wired) coupling 776 in the form of suitable electrical interconnects (e.g., wires) that couple the actuator 772 and the plurality of electrodes 731 to form a closed electrical circuit. The electrodes 731 are arranged in parallel, with the internal actuator 723 sandwiched between one or more upper electrodes 731 and one or more lower electrodes 731 .

[0110] Actuation of the capillary array device 700 is illustrated by the transition from FIG. 7A to FIG. 7B. In this example, the plurality of electrodes 731 are oriented in the transverse (xy) plane. Thus, application of a voltage by the actuator 772 between the plurality of electrodes 731 (and thus across the thickness of the internal actuator 723) compresses the internal actuator 723 in the thickness direction, thereby expanding the internal actuator 723 in the transverse direction (in both the x and y directions). The internal actuator 723 and other components of the capillary array device 700 are mounted such that this actuation causes the internal actuator 723 to move the non-internal actuatable element 727 relative to the plurality of capillaries, in this example, in a direction toward the flexible section 136 (left in FIGS. 7A and 7B), as indicated by the left-pointing arrow in FIG. 7B. This movement then deforms the flexible section 136 according to any of the examples described herein.

[0111] Alternatively, capillary array device 700 may be configured according to any of the other embodiments disclosed herein that include an internal actuator. Thus, internal actuator 723 may be oriented and / or positioned differently, internal actuator 723 may be of a different type (e.g., SMP, SMA, etc.), actuation device 772 may be of a different type (e.g., heat source, light source, magnetic source, etc.), etc.

[0112] FIG. 8 is a schematic diagram of an example sample analysis system (or apparatus, analytical instrument, etc.) 800 according to an embodiment of the present disclosure. The sample analysis system 800 includes one or more capillary array devices as disclosed herein, such as capillary array devices 100, 300, 400, 500, or 600. The sample analysis system 800 is configured to perform optical measurements on samples in a plurality of capillaries 124 (not shown in FIG. 8 ), such as chemical compounds, biological compounds, biological cells, or components thereof. In the context of the present disclosure, the term “optical measurements” encompasses imaging (e.g., microscopic imaging) as well as measurements of more specific properties or attributes (e.g., the presence or absence, concentration, mass, charge, number, size, etc.) of analytes, depending on the type of sample analysis system 800. In various examples, the optical measurements may be based on fluorescence, absorbance, luminescence (including chemiluminescence or bioluminescence), (UV, visible, or IR) spectroscopy, Raman scattering, microscopy, etc. Generally, the structure and operation of the various components included in optical-based sample analysis instruments will be understood by those skilled in the art and, therefore, will only be briefly described herein to facilitate understanding of the subject matter disclosed herein.

[0113] The sample analysis system 800 may include an optical system 106 as described herein. The capillary array device 100 is configured to be loaded into an operating position within the sample analysis system 800 such that the plurality of capillaries 124 (or their windows) supported by the capillary array device 100 are in proper optical alignment with the optical system 106. The optical system 106 includes one or more photodetectors (or cameras) 114 configured to receive and measure emitted light EM emitted from an exposed (optically readable) area of the capillary array device 100. Examples of photodetectors 114 include, but are not limited to, cameras, photomultiplier tubes (PMTs), photodiodes (PDs), charge-coupled devices (CCDs), active pixel sensors (APSs) such as complementary metal-oxide semiconductor (CMOS) devices, etc., that are sensitive to the radiation wavelengths to be detected.

[0114] In some examples (depending on the type of sample analysis system 800), the optical system 106 further includes one or more light sources 110 configured to direct excitation light EX at a selected wavelength(s) to illuminate samples in the plurality of capillaries 124 at an exposure area of the capillary array device 100. Examples of light sources 110 include, but are not limited to, broadband light sources (e.g., flash lamps), light-emitting diodes (LEDs), laser diodes (LDs), lasers, etc. Multiple light sources 110 may be provided to allow a user to select a desired excitation wavelength.

[0115] The optical system 106 may further include various types of emission optics 835 configured to transmit emission light EM from the capillary array device 100 to the photodetector 114, or additionally excitation optics 839 configured to transmit excitation light EX from the light source 110 to the capillary array device 100. Examples of emission optics 835 or excitation optics 835 include, but are not limited to (and as needed and understood by those skilled in the art), lenses, readheads, apertures, optical filters (e.g., including multiple selectable filters), light guides, mirrors, beam splitters, beam steering devices, monochromators, diffraction gratings, prisms, optical path switches, and the like.

[0116] The sample analysis system 800 may include an instrument console (or instrument housing, enclosure, etc.) 843 configured to contain the capillary array device 100, the optical system 106, and other components of the sample analysis system 800, including those associated with the capillary array device 100, such as those shown in FIGS. 1D-1F, 2, and 7A-7F. The instrument console 843 is also configured to prevent stray light from reaching components of the capillaries 124 and the optical system 106 that may be adversely affected by stray light. The instrument console 843 also provides an enclosed environment to allow environmental control (e.g., control of temperature, humidity, air pressure, etc.) within the console as needed. The instrument console 843 may include one or more panels, doors, drawers, etc., for loading / removing the capillary array device 100 and other portable / replaceable components, for providing access to interior areas and components of the sample analysis system 800, etc. As an example, Figure 8 illustrates a door 847 that can be opened to allow the capillary array device 100 (with or without the device support 200) to be loaded into and subsequently removed from the console interior, as indicated by the double arrow 851 in Figure 8. The loading / removal of the capillary array device 100 can be done manually or (semi-)automatically. As described herein, samples and various liquids and / or gels can be pre-loaded into the plurality of capillaries 124 before the capillary array device 100 is installed in the sample analysis system 800 to perform an analysis.

[0117] The sample analysis system 800 may also include an actuator 168 (or 768) including an actuation device 172 (or 772) and a (contact or non-contact) coupling 176 (or 776) according to any of the embodiments described herein. The sample analysis system 800 may also include an HV source 188 configured to apply a voltage (potential difference) across the plurality of capillaries 124 as described herein.

[0118] The sample analysis system 800 may further include a system controller 855 .

[0119] The system controller 855 generally represents one or more electronics-based (e.g., computing) devices or modules that include various types of hardware (e.g., electronics-based processors, memory, non-transitory computer-readable media, etc.), firmware (e.g., integrated circuits or ICs), and / or software configured to perform various functions required to operate the type of sample analysis system 800 provided. The system controller 855 may be embodied as one or more types of hardware, such as a circuit board. The system controller 855 may include data acquisition (collection) circuitry (DAC) configured to receive and process signals output from the photodetector 114 and generate user-interpretable data therefrom that represent the results of the sample analysis. The system controller 855 may also be considered to represent devices configured to control, monitor, and synchronize the operation of various components of the sample analysis system 800, such as the photodetector 114, the emission optics 835 (e.g., if it includes components that consume power or are capable of automatic adjustment), the light source 110, the excitation optics 839 (e.g., if it includes components that consume power or are capable of automatic adjustment), the actuator 168, and the HV source 188. The system controller 855 may also be considered to represent user input and output devices, such as a keyboard, a display monitor, a printer, a graphical user interface (GUI), and the like. The system controller 855 may include an operating system (e.g., Microsoft Windows® software) for controlling and managing various functions of the system controller 855. In one example, the system controller 855 is configured to control or implement all or a portion of any of the methods disclosed herein. For all such purposes, the system controller 855 may communicate with the above components via wired or wireless communication links that enable the transmission of signals (e.g., sending control signals, receiving measurement or feedback signals, etc.).

[0120] An example of a general method for analyzing a sample will now be described, particularly involving the use of a capillary array device 100. A capillary array device 100 containing a sample is provided. In this example, providing the capillary array device 100 includes injecting the sample and one or more liquids and / or gels into a plurality of capillaries 124 according to any of the methods disclosed herein. Providing the capillary array device 100 may also include loading the capillary array device 100 into an operating position within the sample analysis system 800 to place the capillary array device 100 in proper optical alignment with the optical system 106 of the sample analysis system 800. Depending on the type of sample analysis to be performed, the sample may undergo various types of preparation or conditioning (e.g., incubation, mixing, homogenization, centrifugation, buffering, adding reagents, denaturing, lysing, cleaving, deprotecting, etc.) before being placed into the sample analysis system 800, as will be understood by those skilled in the art.

[0121] After providing the capillary array device 100 as previously described, the method includes performing optical measurements of the samples in the plurality of capillaries 124 to obtain optical data from one or more analytes of the sample. In a typical example, performing the optical measurements involves illuminating the sample with excitation light EX and collecting resultant emitted light EM emitted from the sample in response to the illumination. In this example, the optical system 106 of the sample analysis system 800 described above is operated to perform the optical measurements. In some examples, the excitation light EX induces a photoluminescence (e.g., fluorescence or phosphorescence) response in one or more analytes of the sample, and the optical measurements involve measuring the intensity of the photoluminescence light to quantify (e.g., determine the concentration of) the analytes or, additionally, to generate an image of the sample containing the photoluminescent analytes. In other examples, excitation light EX is used to illuminate the sample without necessarily inducing photoluminescence, and emission light EM is used to quantify the analyte by measuring the absorbance of the sample, or additionally to generate an image of the sample.

[0122] In other examples, performing an optical measurement does not require illuminating the sample with excitation light EX. For example, as will be understood by those skilled in the art, a reagent that induces luminescence, such as flash or glow luminescence, may be added to the sample. As another example, a label, such as a stable label or a radioactive label, may be added to the sample, depending on the type of optical measurement to be performed.

[0123] In all such cases, the emission optics 835 of the optical system 106 of the sample analysis system 800 may be operated to collect emitted light EM from the sample and direct the emitted light EM to the photodetector 114. The emitted light EM may be detected either on the same side of the capillary array device 100 as the excitation light EX is incident (e.g., the top side), or on the opposite side (e.g., excitation occurs on the top side, but detection occurs on the bottom side). The photodetector 114 then converts the emitted light EM into an electrical signal (detection or measurement signal) and transmits the electrical signal to signal processing circuitry, such as data acquisition circuitry of the system controller 855, described above.

[0124] In one example, the sample analysis system 800 is configured as a capillary electrophoresis (CE) system. In this case, the plurality of capillaries 124 contains an electrophoretic separation medium (i.e., an analytical separation medium formed for CE). In this example, the electrophoretic separation medium is an electrophoretic polymer gel, which may be a polymer formed for CE as described above. To perform CE, the HV source 188 of the sample analysis system 800 is operated to apply a potential difference across the length of each of the plurality of capillaries 124, as described herein. The HV source 188 represents various components, such as a waveform generator, amplifier, etc., required to apply a potential difference having the desired operating parameters (amplitude / magnitude, frequency, waveform, number of pulses (pulse rate), etc.) for performing CE, as will be understood by those skilled in the art.

[0125] Another example of a method for analyzing a sample, particularly in the context of CE, will now be described. The method may generally include providing a capillary array device 100 and then performing optical measurements of the sample in the plurality of capillaries 124 to obtain optical data from one or more analytes of the sample. In this example, the method further includes applying a potential difference across the plurality of capillaries 124 (typically simultaneously, in parallel, although sequential measurements may also be performed) prior to and / or during the optical measurements. The potential difference induces different analytes to migrate through the electrophoretic separation medium at different rates depending on their different sizes and / or charge states, according to mechanisms commonly understood by those skilled in the art. In this manner, the different analytes become separated from one another, thereby facilitating the optical measurement of one or more target analytes of interest in the sample.

[0126] In another example, another type of analytical separation medium may be utilized within the plurality of capillaries 124, such as, for example, a chromatographic separation medium.

[0127] [Illustrative Embodiments] Exemplary aspects provided in accordance with the presently disclosed subject matter include, but are not limited to, the following.

[0128] 1. A capillary array device comprising: a capillary array holder having a stationary section, a movable section, and a flexible section connecting the stationary section and the movable section; and a plurality of capillaries attached to the capillary array holder, the plurality of capillaries being arranged in parallel and extending along a device axis of the capillary array holder, wherein the movable section is linearly movable along the device axis relative to the capillaries and the stationary section, and the flexible section deforms in response to movement of the movable section.

[0129] 2. A capillary array device according to embodiment 1, comprising a detection area configured to allow transmission of light into and out of the detection area.

[0130] 3. The capillary array device of embodiment 2, wherein the stationary section comprises a detection area.

[0131] 4. The capillary array device of embodiment 2, wherein the movable zone comprises a detection area.

[0132] 5. A capillary array device according to any one of aspects 1 to 4, wherein the capillary array holder has an overall length (total length) along the device axis, and the stationary section, the movable section, and the flexible section are arranged such that movement of the movable section changes the overall length.

[0133] 6. A capillary array device according to any one of aspects 1 to 5, wherein the capillary array holder comprises a plurality of wells configured to contain respective liquids or gels, the plurality of wells being arranged such that each capillary is aligned (lined up) with each of the wells along the axis of the device, and each capillary is movable in and out of each well (capable of entering and exiting each well) in response to movement of the movable area.

[0134] 7. The capillary array device of embodiment 6, wherein the working area comprises a plurality of wells.

[0135] 8. The capillary array device of embodiment 6, wherein the stationary area comprises a plurality of wells.

[0136] 9. A capillary array device according to any one of aspects 6 to 8, wherein the plurality of capillaries each have a first capillary end and a second capillary end opposite the first capillary end along the device axis, and the movable zone is configured to move from a first position where the first capillary end is outside the well to a second position where the first capillary end is inside the well.

[0137] 10. The capillary array device according to any one of aspects 6 to 9, wherein the capillary array holder includes a plurality of electrodes, each of which is disposed in one of the plurality of wells.

[0138] 11. A capillary array device according to any one of aspects 1 to 10, wherein the plurality of capillaries are arranged side by side along a horizontal axis perpendicular to the device axis, the capillary array holder has a recess extending along the horizontal axis and configured to contain a liquid or gel, and the recess is sufficiently wide along the horizontal axis to simultaneously accommodate all of the plurality of capillaries.

[0139] 12. The capillary array device of embodiment 11, wherein the movable area comprises a recess.

[0140] 13. The capillary array device of embodiment 11, wherein the stationary area comprises a recess.

[0141] 14. The capillary array device according to any one of aspects 11 to 13, wherein the capillary array holder includes an electrode disposed in the recess.

[0142] 15. A capillary array device according to any one of aspects 1 to 14, wherein the capillaries are arranged side by side along a horizontal axis perpendicular to the device axis, each of the capillaries having a first capillary end and a second capillary end opposite the first capillary end along the device axis, the capillary array holder has a plurality of wells configured to contain a respective liquid or gel, the plurality of wells are arranged such that each first capillary end is aligned (lined up) with a respective one of the plurality of wells along the device axis, the plurality of first capillary ends are movable in and out of each well (are able to enter and exit the wells) in response to movement of the movable area, the capillary array holder has a recess extending along the horizontal axis, and the capillary array holder has a configuration according to one of (a) the second capillary ends are arranged in the recess in a fixed state (in a fixed manner), or (b) the first capillary ends are movable in and out of the recess (are able to enter and exit the recess) in response to movement of the movable area.

[0143] 16. A capillary array device according to aspect 15, wherein the capillary array holder comprises a plurality of electrodes, at least one electrode being disposed within each of the plurality of wells, and at least one other electrode being disposed within the recess.

[0144] 17. The capillary array device of aspect 15 or 16, wherein the movable area comprises a plurality of wells and the stationary area comprises a recess.

[0145] 18. A plurality of capillaries are arranged side by side along a horizontal axis perpendicular to a device axis, each of the plurality of capillaries having a first capillary end and a second capillary end opposite the first capillary end along the device axis, the capillary array holder has a plurality of wells configured to contain a respective liquid or gel, the plurality of wells are arranged such that each first capillary end is aligned (lined up) with a respective one of the plurality of wells along the device axis, and the plurality of first capillary ends are movable into and out of the respective wells (wells) in response to movement of the movable region. 18. The capillary array device according to any one of aspects 1 to 17, wherein the capillary array holder comprises a first recess, the first recess being aligned (side by side) with the plurality of first capillary ends along the horizontal axis, the plurality of first capillary ends being movable in and out of the first recess (being able to enter and exit the first recess) in response to movement of the movable area, and the capillary array holder comprises a second recess extending along the horizontal axis and configured to receive the plurality of second capillary ends.

[0146] 19. The capillary array device of aspect 18, wherein the movable area comprises a plurality of wells and a first recess, and the stationary area comprises a second recess.

[0147] 20. A capillary array device according to aspect 18 or 19, wherein the movable area is configured to move between a first position, a second position, and a third position, wherein in the first position, the first capillary end is outside the well and the first recess, in the second position, the first capillary end is inside the well, and in the third position, the first capillary end is inside the first recess.

[0148] 21. A capillary array device according to any of aspects 18 to 20, wherein the movable area is a first movable area having a plurality of wells and a first recess, the capillary array holder further comprises a second movable area that is linearly movable in parallel along the device axis relative to the plurality of capillaries and the stationary area, and the ends of the plurality of second capillaries are movable in and out of the second recess (capable of entering and exiting the second recess) in response to movement of the second movable area.

[0149] 22. The capillary array device of embodiment 21, wherein the second movable region comprises a second recess.

[0150] 23. A capillary array device according to aspect 21 or 22, wherein the capillary array holder further comprises a third recess extending along the horizontal axis, and the plurality of first capillary ends are movable in and out of the third recess (are capable of entering and exiting the third recess) in response to movement of the first movable area.

[0151] 24. The capillary array device of aspect 23, wherein the first movable area is configured to move between a first position, a second position, and a third position, and wherein at the first position, the first capillary end is within the first recess, at the second position, the first capillary end is within the third recess, and at the third position, the first capillary end is within the well.

[0152] 25. The capillary array device of embodiment 24, wherein the second movable section is configured to move to a third position in which the second capillary end is within the second recess.

[0153] 26. The capillary array device of any of aspects 1-25, wherein the stationary section and / or the movable section comprises a guide feature configured to guide movement of the movable section.

[0154] 27. A capillary array device as described in aspect 26, wherein the guide feature comprises a leg extending from at least one of the stationary section or the movable section, the leg extending along the device axis and adjacent to the other of the stationary section or the movable section.

[0155] 28. A capillary array device as described in embodiment 27, wherein the guide feature comprises a recess that is axially aligned with the leg, and in response to movement of the movable region, the leg either moves into the recess or the recess moves around and adjacent to the leg.

[0156] 29. The capillary array device of any one of aspects 1-28, wherein the flexible section comprises a compliant spring configured to bias the movable member in a direction along the device axis.

[0157] 30. A capillary array device according to any one of aspects 1 to 29, wherein at least a portion of the flexible section is made of a material that is more flexible (has flexibility) than the material of the stationary section and the movable section.

[0158] 31. The capillary array device of any of aspects 1-30, wherein at least a portion of the flexible section has an open-frame configuration.

[0159] 32. A capillary array device according to embodiment 31, wherein the open frame configuration comprises a plurality of structural members defining a plurality of holes extending through (through) the flexible section.

[0160] 33. The capillary array device of any of aspects 1-32, wherein at least a portion of the flexible section is sandwiched between the stationary section and the movable section along the device axis.

[0161] 34. The capillary array device of any of aspects 1-33, wherein at least a portion of the flexible section is sandwiched between the stationary section and the movable section along a transverse axis perpendicular to the device axis.

[0162] 35. The capillary array device of any of aspects 1-34, wherein the movable area comprises a feature configured to be coupled to or contacted by an actuator.

[0163] 36. The capillary array device according to any one of aspects 1 to 35, comprising an actuator configured to move the movable region.

[0164] 37. The capillary array device of embodiment 36, wherein the actuator comprises an actuation device and a mechanical linkage coupled to the actuation device and coupled to or contactable with the movable region.

[0165] 38. The capillary array device of embodiment 36, wherein the actuator comprises an internal actuator and an actuation device configured to trigger actuation of the internal actuator.

[0166] 39. The capillary array device of embodiment 38, wherein the internal actuator is selected from the group consisting of a dielectric elastomer actuator, a shape memory polymer, a shape memory alloy, and a magnet.

[0167] 40. The capillary array device of aspect 38 or 39, wherein the actuation device is selected from the group consisting of a voltage source, a heat source, a light source, and a magnetic source.

[0168] 41. The capillary array device according to any one of aspects 38 to 40, wherein the movable section and / or the flexible section comprises an internal actuator.

[0169] 42. A sample analysis system comprising: a capillary array device according to any one of aspects 1 to 41; and a photodetector positioned in optical alignment with the plurality of capillaries to receive light emitted from the plurality of capillaries.

[0170] 43. The sample analysis system of embodiment 42, comprising a light source positioned in optical alignment with the detection area to transmit light to the plurality of capillaries.

[0171] 44. The sample analysis system of aspect 42 or 43, comprising a voltage source configured to apply a potential difference across the plurality of capillaries.

[0172] 45. The sample analysis system of aspect 44, wherein the voltage source is configured to apply a potential difference according to operating parameters effective to perform capillary electrophoresis on samples disposed in the plurality of capillaries.

[0173] 46. The sample analysis system of any of aspects 42-45, comprising an actuator configured to actuate (activate) movement of the movable section.

[0174] 47. The sample analysis system of aspect 46, wherein the actuator comprises a feature selected from the group consisting of a mechanical or electromechanical actuator coupled to a movable mechanical linkage, a voltage source, a heat source, a light source, and a magnetic source.

[0175] 48. The sample analysis system of any of aspects 42-47, comprising a device support configured to support the capillary array device in a fixed position.

[0176] 49. A method for injecting a liquid or gel into a plurality of capillaries, the method comprising the steps of: providing a capillary array device comprising a plurality of capillaries and a capillary array holder, the capillary array holder comprising a stationary section, a movable section, and a flexible section connecting the stationary section and the movable section, the plurality of capillaries being attached to the capillary array holder and arranged in parallel and extending along a device axis of the capillary array holder; moving the movable section along the device axis to a position where the plurality of capillaries extend into one or more receptacles of the capillary array holder, the liquid or gel being contained in the one or more receptacles and the flexible section deforming in response to movement of the movable section; and injecting the liquid or gel from the one or more receptacles into the capillaries by capillary action.

[0177] 50. The method of embodiment 49, wherein the injecting step includes applying a voltage across each of the plurality of capillaries along the device axis to electrokinetically assist the injection.

[0178] 51. The method of aspect 49 or 50, comprising, after the injecting step, applying a voltage across each of the plurality of capillaries along the device axis to electrokinetically induce the liquid or gel in each capillary to flow through the capillary.

[0179] 52. The method of any one of aspects 49 to 51, wherein the plurality of storage portions each store a sample to be analyzed, and the injecting step includes injecting the sample into the plurality of capillaries, respectively.

[0180] 53. The method of aspect 52, comprising, after the injecting step, applying a voltage across each of the plurality of capillaries along the device axis, the voltage being applied according to operating parameters effective to perform capillary electrophoresis on the sample.

[0181] 54. The method of any of aspects 49-53, wherein the one or more receptacles comprise a plurality of wells, and each capillary is aligned with a respective one of the plurality of wells along the device axis.

[0182] 55. The method of any one of aspects 49-54, wherein the one or more containers comprise recesses, and after the moving step, each of the plurality of capillaries extends into (enters) the recesses.

[0183] 56. The plurality of capillaries have respective first capillary ends and second capillary ends, the one or more storage units have a plurality of wells, the plurality of first capillary ends are movable in and out of the respective wells (are capable of entering or exiting the wells) in accordance with movement of the movable area, the liquid or gel injected from the plurality of wells is a first liquid or a first gel injected through the plurality of first capillary ends, and the capillary array holder is a second 56. A method according to any one of aspects 49 to 55, wherein the device further comprises one of the following steps: (a) injecting the second liquid or second gel into the ends of the plurality of second capillaries by capillary action; (b) moving the movable area along the axis of the device to a position where the ends of the plurality of first capillaries extend (enter) into the recess; and (c) injecting the second liquid or second gel into the ends of the plurality of first capillaries by capillary action.

[0184] 57. The method of any of aspects 49-56, wherein the plurality of capillaries have respective first and second capillary ends, the one or more storage portions have a plurality of wells, the plurality of first capillary ends are movable in and out of the respective wells (capable of entering and exiting the wells) in accordance with movement of the movable area, the liquid or gel injected from the plurality of wells is a first liquid or a first gel injected through the plurality of first capillary ends, the capillary array holder has a first recess for accommodating a second liquid or a second gel, and the capillary array holder has a second recess for accommodating a third liquid or a third gel, and the method further comprises the steps of injecting the second liquid or the second gel into the plurality of first capillary ends by capillary action, and injecting the third liquid or the third gel into the plurality of second capillary ends by capillary action.

[0185] 58. The method of embodiment 57, wherein the movable area is a first movable area, the capillary array holder has a second movable area, and before injecting a third liquid or a third gel into the ends of the plurality of second capillaries, the second movable area is moved along the device axis to a position where the ends of the plurality of second capillaries extend (enter) into the second recess.

[0186] 59. The method of aspect 58, wherein the capillary array holder has a third recess for accommodating a fourth liquid or a fourth gel, and the method further includes a step of injecting the fourth liquid or the fourth gel into the ends of the plurality of first capillaries by capillary action after injecting the second liquid or the second gel into the ends of the plurality of first capillaries.

[0187] 60. A method according to any one of aspects 49 to 59, wherein the movement of the movable area is performed manually.

[0188] 61. The method of any one of aspects 49-59, wherein moving the movable section comprises actuating (activating) the movement of the movable section.

[0189] 62. The method of aspect 61, wherein actuating comprises moving an actuator into contact with the movable section or actuating an actuator coupled to the movable section.

[0190] 63. The method of embodiment 61, wherein actuating comprises magnetically coupling an actuator with a magnet of the capillary array holder.

[0191] 64. The method of embodiment 61, wherein actuating comprises activating an internal actuator of the capillary array holder.

[0192] 65. The method of embodiment 64, wherein the activating is selected from the group consisting of: (a) applying an electric field to an internal actuator comprising a dielectric elastomer actuator; (b) applying thermal energy to an internal actuator comprising a shape memory polymer; (c) applying a light beam to an internal actuator comprising a shape memory polymer; (d) applying an electric field to an internal actuator comprising a shape memory polymer; (e) applying a magnetic field to an internal actuator comprising a shape memory polymer; or (f) applying thermal energy to an internal actuator comprising a shape memory alloy.

[0193] 66. A method for analyzing a sample, the method comprising: injecting a liquid or gel into a plurality of capillaries according to the method of any one of aspects 49 to 65, wherein the liquid or gel contains a sample to be analyzed, and the injecting step comprises injecting the sample into each of the plurality of capillaries; and performing optical measurements of the sample in the plurality of capillaries to obtain optical data from one or more analytes in the sample.

[0194] 67. The method of embodiment 66, wherein the step of performing optical measurements includes detecting emitted light emitted from the plurality of capillaries.

[0195] 68. The method of aspect 66 or 67, wherein the step of performing optical measurements includes illuminating the sample with excitation light.

[0196] 69. The method of any one of aspects 66-68, comprising separating the sample in each capillary for analysis before and / or during optical measurements.

[0197] 70. The method of embodiment 69, wherein the analytical separation of the sample comprises performing capillary electrophoresis on the sample.

[0198] It should be understood that terms such as "communicate" and "in communication" (e.g., a first component "communicates" or "is in communication" with a second component) are used herein to indicate a structural, functional, mechanical, electrical, signal, optical, magnetic, electromagnetic, ionic, or fluid relationship between two or more components or elements. As such, saying that one component is in communication with a second component is not intended to exclude the possibility that additional components may be present between the first and second components and / or may be operatively associated or engaged with the first and second components.

[0199] It should be understood that various aspects or details of the invention may be changed without departing from the scope of the invention. Furthermore, the foregoing description is for purposes of illustration only, and not of limitation, the present invention being defined by the claims.

Claims

1. A capillary array device, a capillary array holder; a plurality of capillaries attached to the capillary array holder; Equipped with the capillary array holder comprises a stationary section, a movable section, and a flexible section, the flexible section connecting the stationary section and the movable section; the plurality of capillaries are arranged in parallel and extend along an apparatus axis of the capillary array holder; the movable section is linearly movable along the device axis relative to the plurality of capillaries and the stationary section; The flexible section deforms in response to movement of the movable section.

2. 2. The capillary array device according to claim 1, wherein the capillary array holder comprises a plurality of wells configured to contain respective liquids or gels, the plurality of wells being arranged such that each capillary is aligned with a respective one of the plurality of wells along the device axis, and the plurality of capillaries are capable of entering and exiting each well in response to movement of the movable area.

3. each of the plurality of capillaries having a first capillary end and a second capillary end opposite the first capillary end along the device axis; 3. The capillary array device of claim 2, wherein the movable section is configured to move from a first position in which the first capillary end is located outside the well to a second position in which the first capillary end is located within the well.

4. 3. The capillary array device according to claim 2, wherein the capillary array holder comprises a plurality of electrodes, each electrode being disposed inside a respective one of the plurality of wells.

5. the plurality of capillaries are arranged side by side along a horizontal axis perpendicular to the device axis; 2. The capillary array device of claim 1, wherein the capillary array holder comprises a recess extending along the horizontal axis and configured to contain a liquid or gel, the recess being sufficiently wide along the horizontal axis to simultaneously receive all of the plurality of capillaries.

6. The capillary array device according to claim 5 , wherein the capillary array holder includes an electrode disposed in the recess.

7. the plurality of capillaries are arranged side by side along a horizontal axis perpendicular to the device axis; each of the plurality of capillaries having a first capillary end and a second capillary end opposite the first capillary end along the device axis; the capillary array holder comprises a plurality of wells, each well configured to contain a respective liquid or gel, the plurality of wells being arranged such that each first capillary end is aligned with a respective one of the plurality of wells along the device axis, and each first capillary end is capable of moving into and out of each well in response to movement of the movable zone; the capillary array holder includes a recess extending along the transverse axis; 2. The capillary array device according to claim 1, wherein the capillary array holder has a configuration according to one of the following (a) and (b). (a) The second capillary end is fixedly disposed within the recess. (i) The first capillary end can move in and out of the recess in response to movement of the movable region.

8. the plurality of capillaries are arranged side by side along a horizontal axis perpendicular to the device axis; each of the plurality of capillaries having a first capillary end and a second capillary end opposite the first capillary end along the device axis; the capillary array holder comprises a plurality of wells, each well configured to contain a respective liquid or gel, the plurality of wells being arranged such that each first capillary end is aligned with a respective one of the plurality of wells along the device axis, and each first capillary end is capable of moving into and out of each well in response to movement of the movable zone; the capillary array holder includes a first recess, the first recess being disposed along the transverse axis alongside a plurality of the first capillary ends, the first capillary ends being movable into and out of the first recess in response to movement of the movable section; 2. The capillary array device according to claim 1, wherein the capillary array holder comprises a second recess, the second recess extending along the transverse axis and configured to receive the second capillary end.

9. the movable section is configured to move between a first position, a second position, and a third position; at the first position, the first capillary end is located outside the well and the first recess; At the second position, the first capillary end is located within the well; 9. The capillary array device according to claim 8, wherein the first capillary end is located within the first recess at the third position.

10. the movable section is a first movable section comprising the well and the first recess; the capillary array holder further comprises a second movable section linearly movable along the device axis relative to the plurality of capillaries and the stationary section; The capillary array device according to claim 8 , wherein the second capillary end is capable of moving into and out of the second recess in response to movement of the second movable region.

11. the capillary array holder further comprises a third recess extending along the horizontal axis; The capillary array device according to claim 10 , wherein the first capillary end is capable of moving into and out of the third recess in response to movement of the first movable region.

12. the first movable section is configured to move between a first position, a second position, and a third position; At the first position, the first capillary end is located within the first recess; At the second position, the first capillary end is located within the third recess; The capillary array device according to claim 11 , wherein the first capillary end is located within the well at the third position.

13. The capillary array device of claim 12 , wherein the second movable section is configured to move to the third position, and in the third position, the second capillary end is located within the second recess.

14. 2. The capillary array device according to claim 1, wherein the flexible section includes at least one of the following characteristics (a) to (f): (a) The flexible section comprises a compliant spring configured to bias the movable member in a direction along the device axis. (i) At least a portion of the flexible section is made of a material that is more flexible than the material of the stationary section and the movable section. (c) at least a portion of the flexible section has an open frame configuration; (d) at least a portion of the flexible section has an open-frame configuration, the open-frame configuration comprising a plurality of structural members defining a plurality of holes extending through the flexible section; (e) At least a portion of the flexible section is sandwiched between the stationary section and the movable section along the device axis. (f) at least a portion of the flexible section is sandwiched between the stationary section and the movable section along a transverse axis perpendicular to the device axis;

15. The capillary array device of claim 1 , comprising an actuator configured to move the movable section.

16. 16. The capillary array device according to claim 15, wherein the actuator includes at least one of the following features (a) to (e): (a) an actuator and a mechanical link coupled to the actuator and coupled to or contactable with the movable section; (i) an internal actuator and an actuation device configured to induce actuation of said internal actuator; (c) An internal actuator and an actuation device configured to induce actuation of the internal actuator, wherein the internal actuator is selected from the group consisting of a dielectric elastomer actuator, a shape memory polymer, a shape memory alloy, and a magnet. (d) an internal actuator and an actuation device configured to induce actuation of said internal actuator, said actuation device being selected from the group consisting of a voltage source, a heat source, a light source, and a magnetic source. (e) an internal actuator and an actuation device configured to trigger actuation of the internal actuator, wherein the movable section and / or the flexible section comprises the internal actuator;

17. 10. The capillary array device of claim 1, comprising a plurality of electrodes configured to apply a potential difference to samples disposed in the plurality of capillaries according to operating parameters effective to perform capillary electrophoresis.

18. 1. A sample analysis system comprising: The capillary array device according to claim 1 ; a photodetector positioned in optical alignment with the plurality of capillaries to receive light emitted from the plurality of capillaries; A sample analysis system comprising:

19. 1. A method for injecting a liquid or gel into a plurality of capillaries, comprising: The capillary array device includes a plurality of capillaries and a capillary array holder. the capillary array holder comprises a stationary section, a movable section, and a flexible section, the flexible section connecting the stationary section and the movable section; the plurality of capillaries are attached to the capillary array holder, the plurality of capillaries are arranged in parallel and extend along an apparatus axis of the capillary array holder; the liquid or gel is contained in one or more containers of the capillary array holder, and the flexible section deforms in response to movement of the movable section; The method comprises: providing the capillary array device; moving the movable section along the device axis to a position where the plurality of capillaries enter the one or more reservoirs; and injecting the liquid or gel from the one or more reservoirs into the plurality of capillaries by capillary action; A method comprising:

20. 1. A method for analyzing a sample, comprising: Injecting the liquid or gel containing the sample to be analyzed into the capillaries according to the method of claim 19; and performing optical measurements of the sample in the plurality of capillaries to obtain optical data from one or more analytes in the sample; Including, The method, wherein the injecting includes individually injecting the sample into the plurality of capillaries.

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