Flexible capillary array devices and related systems and methods
By designing a capillary array holder with fixed segments, movable segments and flexible segments, the high cost and design limitations in manufacturing and design of existing capillary array devices are solved, and the service life of the analytical separation media is extended.
Patent Information
- Application Number
- CN202380051881.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Priority Date
- 2022-07-12
- Filing Date
- 2023-05-08
- Publication Date
- 2025-04-29
AI Technical Summary
Existing capillary array devices have problems with expensive microfluidic chip manufacturing costs and design limitations in manufacturing and design, and capillary preloaded analytical separation media have problems with storage life and degradation.
A capillary array holder including a fixed section, a movable section and a flexible section is designed to allow the capillary to move linearly along the axis of the device and to achieve parallel arrangement and flexible movement of the capillary by flexing the flexible section.
The device improves the flexibility and mobility of the capillary array by reducing manufacturing costs and design limitations, extends the service life of the analytical separation media, and solves the problems of storage life and degradation.
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Figure CN119907919A_ABST
Abstract
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. Provisional Patent Application Serial No. 63 / 388,593, filed on July 12, 2022, entitled “FLEXIBLECAPILLARY ARRAY DEVICE AND RELATED SYSTEMS AND METHODS,” under 35 U.S.C. §119(e), the entire contents of which are incorporated herein by reference. Technical Field
[0002] The present invention generally relates to a capillary array device for maintaining a parallel arrangement of capillaries. Specifically, the present invention relates to a capillary array device having a flexible component that allows a portion of the device to move relative to the capillaries. The capillaries can be used to hold samples to be detected or measured by an optical device-based instrument. The capillaries can be used, for example, for capillary electrophoresis (CE). Background Art
[0003] For various purposes, analytical instruments generally utilize capillaries (i.e., tubes with micrometer-scale pores) to contain and transport fluids (in liquid or gas phase) containing samples. In some analytical instruments, the capillary or at least the optically transparent portion of the capillary (referred to as the capillary window) can be used as a sample detection pool. In this case, the analytical instrument is configured to perform optical-based measurements (e.g., fluorescence, absorbance, imaging, etc.) of the analyte of the sample (i.e., the sample component of interest, such as a chemical compound or a biological compound) contained in the capillary by reading the electromagnetic energy emitted from the sample. This emission can be in response to the sample being irradiated by an electromagnetic energy beam directed to the capillary (window) by a light source of the analytical instrument. In some analytical instruments, the capillary can include a separation medium in its lumen (inner pore), which is formulated to separate different analytes of the sample based on different characteristics or properties (such as molecular size, molecular composition, charge, etc.). In some analytical techniques, the separation medium can be fixed (i.e., stationary phase) in the capillary. In this case, the sample is carried through the capillary by a fluid (i.e., a mobile phase, such as one or more solvents) and in contact with a separation medium. As the sample migrates through the separation medium, different analytes of the sample become separated from each other, thereby facilitating the 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, each of which contains a separate sample. In this case, the analytical instrument can be configured to read or otherwise illuminate multiple capillaries simultaneously.
[0005] Many parts of CE system or other analysis and separation system can be realized in microfluid scale, which means that one or more dimensions of such parts are micron-sized, or other dimensions are millimeter-sized in addition. Therefore, many parts in these parts can be implemented in / on one or more microfluidic chips or be connected thereto. Typically, the conduit (and chamber or other enclosed space) provided for conveying fluid is the channel formed between the glass layers of microfluidic chip. This microfluidic chip is manufactured by glass using glass etching and glass bonding technology usually. The manufacture of these microfluidic chips is expensive, and the design of microfluidic chips is subject to the limitation of its available manufacturing technology (for example, 2.5-D design limitation caused by required etching step). In addition, complicated procedures are usually required to prepare the microfluidic chip used for analytical instrument. Such procedures can include the fluid conduit and chamber (for example, by operating the perfusion station outside the analytical instrument) of the microfluidic chip with fluid perfusion, and the fluid handling system involving various liquids or gel reservoirs, pipe fittings, pumps, valves, etc., is transported to the microfluidic chip by liquid and gel. Additionally, capillaries are typically preloaded with analytical separation media (eg, CE gels, chromatography stationary phases, etc.), which leads to problems related to limited shelf life and degradation of the analytical separation media.
[0006] There is a continuing need to provide capillary array devices that address challenges such as those described above and / or provide other advantages in performing analytical runs on samples in capillaries. Summary of the invention
[0007] To fully or partially address the aforementioned problems and / or other problems that may have been observed by those skilled in the art, the present disclosure provides methods, processes, systems, devices, instruments and / or apparatus, as described by way of example in the implementations set forth below.
[0008] According to an embodiment, a capillary array device includes: a capillary array holder, the capillary array holder including a fixed section, a movable section, and a flexible section connecting the fixed section and the movable section; and a plurality of capillaries attached to the capillary array holder, wherein the capillaries are arranged in parallel along a device axis of the capillary array holder and are elongated, and wherein: the movable section can move linearly along the device axis relative to the capillaries and the fixed section; and the flexible section flexes in response to the movement of the movable section.
[0009] In an embodiment, the capillary array device further comprises a voltage source configured to apply a potential difference across the capillaries.
[0010] In embodiments, the voltage source is configured to apply a potential difference according to operating parameters effective for performing capillary electrophoresis on a sample disposed in the capillary.
[0011] According to another embodiment, a sample analysis system includes: a capillary array device according to any one of the embodiments disclosed herein; and a light detector positioned to be optically aligned with the capillary to receive light emitted from the capillary.
[0012] In embodiments, the sample analysis system further comprises a voltage source configured to apply a potential difference across the capillary.
[0013] In embodiments, the voltage source is configured to apply a potential difference according to operating parameters effective for performing capillary electrophoresis on a sample disposed in the capillary.
[0014] According to another embodiment, a method for injecting a liquid or a gel into a plurality of capillaries comprises: providing a capillary array device comprising the plurality of capillaries and a capillary array holder, wherein the capillary array holder comprises a fixed section, a movable section and a flexible section connecting the fixed section and the movable section, and the capillaries are attached to the capillary array holder and arranged in parallel along a device axis of the capillary array holder and are elongated; moving the movable section along the device axis to a position at which the capillaries extend into one or more containers of the capillary array holder, wherein the liquid or gel is contained in the one or more containers and the flexible section flexes in response to the movement of the movable section; and injecting the liquid or gel from the one or more containers into the capillaries by capillary action.
[0015] In an embodiment, the container respectively contains a sample to be analyzed, and the injecting comprises respectively injecting the sample into the capillary.
[0016] In embodiments, the method further comprises applying a voltage across each of the capillaries along the device axis after the injecting, wherein the voltage is applied according to operating parameters effective for performing capillary electrophoresis on the sample.
[0017] According to another embodiment, a method for analyzing a sample comprises: injecting the liquid or gel into the capillary according to any of the embodiments disclosed herein, wherein the liquid or gel comprises a sample to be analyzed, and the injection comprises injecting the sample into the capillary accordingly; and optically measuring the sample in the capillary to obtain optical data from one or more analytes of the sample.
[0018] In embodiments, the method further comprises analytically separating the sample in each capillary prior to and / or during performing the optical measurement.
[0019] In embodiments, analytically separating said sample comprises subjecting said sample to capillary electrophoresis.
[0020] By examining the following drawings and detailed description, other devices, apparatuses, systems, methods, features and advantages of the present invention will be or will become clear to those skilled in the art. All these additional systems, methods, features and advantages are intended to be included in this description, within the scope of the present invention, and protected by the appended claims. BRIEF DESCRIPTION OF THE DRAWINGS
[0021] The present invention may be better understood by referring to the following drawings. The components in the drawings are not necessarily to scale, but emphasis is placed on illustrating the principles of the present invention. In the drawings, like reference numerals refer to corresponding parts throughout the different views.
[0022] Figure 1A is a top plan view of an example of a capillary array device according to an embodiment of the present disclosure, the capillary array device being shown in a first position.
[0023] Figure 1B yes Figure 1A A top plan view of a capillary array device is illustrated, the capillary array device being shown in a second position.
[0024] Figure 1C yes Figure 1A A top plan view of a capillary array device is illustrated, the capillary array device being shown in a third position.
[0025] Figure 1D According to the embodiments of the present disclosure Figure 1A A longitudinal side elevation view of a capillary array device is illustrated, the capillary array device shown coupled to an actuator.
[0026] Figure 1E According to the embodiments of the present disclosure Figure 1AA longitudinal side elevation view of a capillary array device is illustrated, the capillary array device being shown coupled to a circuit.
[0027] Figure 1F According to the embodiments of the present disclosure Figure 1A A longitudinal side elevation view of a capillary array device is illustrated, shown coupled to an optics-based measurement device.
[0028] Figure 2 According to the embodiments of the present disclosure Figure 1A An exploded view of an example of a capillary array device and device support is shown.
[0029] Figure 3 is a longitudinal side elevation view of another example of a capillary array device according to another embodiment of the present disclosure.
[0030] Figure 4A is a top perspective view of another example of a capillary array device according to another embodiment of the present disclosure.
[0031] Figure 4B yes Figure 4A A top plan view of a capillary array device is shown.
[0032] Figure 4C is along Figure 4B The line AA shown is taken Figure 4A A cutaway perspective top view of a capillary array device is shown.
[0033] Figure 4D is along Figure 4B The line AA shown is taken Figure 4A A cutaway longitudinal side elevation view of a capillary array device is shown.
[0034] Figure 4E yes Figure 4A A top plan view of a capillary array device is illustrated, the capillary array device being shown in a first position.
[0035] Figure 4F yes Figure 4A A top plan view of a capillary array device is illustrated, the capillary array device being shown in a first position.
[0036] Figure 4G yes Figure 4A A top plan view of a capillary array device is illustrated, the capillary array device being shown in a first position.
[0037] Figure 5Ais a top perspective view of another example of a capillary array device according to another embodiment of the present disclosure.
[0038] Figure 5B yes Figure 5A A top plan view of a capillary array device is shown.
[0039] Fig. 6A is a top perspective view of another example of a capillary array device according to another embodiment of the present disclosure.
[0040] Figure 6B yes Fig. 6A A top plan view of a capillary array device is shown.
[0041] Fig. 7A is a longitudinal side elevation view of another example of a capillary array device according to another embodiment of the present disclosure, the capillary array device being shown in an unactuated position.
[0042] Figure 7B yes Fig. 7A A longitudinal side elevation view of a capillary array device is illustrated, the capillary array device being shown in an actuated position.
[0043] Figure 8 is a schematic diagram of an example of a sample analysis system according to an embodiment of the present disclosure.
[0044] The illustrations in all the drawings are to be regarded as schematic unless specifically noted otherwise. DETAILED DESCRIPTION
[0045] In the present disclosure, all "aspects," "examples," and "embodiments" described are considered to be non-limiting and non-exclusive. Thus, the fact that a particular "aspect," "example," or "embodiment" is explicitly described herein does not exclude other "aspects," "examples," and "embodiments" from the scope of the present disclosure, even if not explicitly described. In the present disclosure, the terms "aspects," "examples," and "embodiments" are used interchangeably, i.e., are considered to have interchangeable meanings.
[0046] In the present disclosure, the terms "substantially", "approximately" or "about" when modifying a particular numerical value may be deemed to encompass a range of values including + / - 10% of this numerical value.
[0047] In the context of the present disclosure, the term "light" refers to electromagnetic energy (i.e., photons) in a general sense, and is therefore not limited to electromagnetic energy only in the visible range. Depending on the embodiment, the wavelength range transmitted to the capillary or emitted from the capillary can 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 the present disclosure, the ultraviolet range is considered to span from 10 nanometers (nm) to 400nm, the visible range is considered to span from 400nm to 700nm, and the infrared range is considered to span from 700nm to 1000nm (1 millimeter (mm)), it should be appreciated that the aforementioned ranges may be slightly different and / or may overlap slightly, depending on the technical source relied on by reference or limitation.
[0048] Figure 1A-1F A non-exclusive example of a capillary array device 100 according to an embodiment of the present disclosure is shown. For reference and description purposes, Figure 1A-1F (and other drawings) include an arbitrarily positioned Cartesian coordinate (xyz) frame. The x-axis, y-axis, and z-axis are also referred to herein as the device axis (or capillary axis), transverse axis, and elevation axis, respectively. The xy plane is referred to herein as the device plane (or capillary plane). The yz plane is referred to herein as the transverse plane. The dimensions along the x-axis, y-axis, and z-axis are respectively considered as length, width, and height (or thickness). Also for reference and description purposes, it is assumed that the xy plane is a horizontal plane relative to the ground (i.e., the surface where the capillary array device 100 or the instrument on which the capillary array device 100 is mounted is placed), and it is assumed that the z-axis is a vertical direction. However, more generally, the capillary array device 100 is not limited to any specific orientation relative to the ground. In the context of the present disclosure, the term "axial" refers to the device axis (x-axis), unless otherwise specified or the context otherwise indicates.
[0049] Figure 1A is a top plan view of capillary array device 100. In this example, capillary array device 100 generally has an overall planar geometry (i.e., is shaped as a plate, chip, etc.) and is elongated along a device axis (x-axis). That is, the largest overall dimension of capillary array device 100 is its length, although capillary array device 100 is not limited to such a geometry. Generally, capillary array device 100 has a first axial end 104 and an axially opposite second axial end 108, the first axial end and the second axial end defining the overall length of capillary array device 100. Capillary array device 100 further has a top side 112 and a bottom side 116 ( Figure 1D). In the context of the present disclosure, the terms "top" and "bottom" are merely relative to each other to distinguish them from each other and are not intended to limit capillary array device 100 to any particular orientation relative to the ground or relative to any other reference.
[0050] In general, 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 capillaries 124 in a parallel arrangement. In this arrangement, the capillaries 124 are elongated along the device axis, spaced apart from each other along the transverse axis, and are held in a fixed position and at a fixed distance from each other. For this purpose, the capillary array holder 120 may include grooves or channels at different positions (not shown, but further described below) that receive the capillaries 124 and may also guide the relative movement between the capillary array holder 120 (a portion thereof) and the capillaries 124, as described below. In the present example, four capillaries 124 are provided, but the capillary array device 100 may include any number of capillaries 124.
[0051] The capillary array holder 120 is defined by a material structural frame or body. The body may be one-piece (monomeric) or may include two or more parts attached (e.g., bonded, adhered, welded, etc.) or fastened (e.g., mechanically) together. The capillary array holder 120 (body) may include one or more fixed segments 128, one or more movable segments 132, and one or more flexible segments (or flexible couplings) 136 coupled to the one or more fixed segments 128 and / or the one or more movable segments 132. The one or more fixed segments 128 are configured to be fixed in place, such as by being appropriately mounted to a device support or receiver, which is part of an associated analytical instrument or is then mounted to / in the analytical instrument. The one or more movable segments 132 are configured to have at least one degree of freedom of movement, particularly a degree of freedom of movement along the device axis, which at least one degree of freedom of movement can be achieved and guided by a suitably configured device support. Figure 1A The double-headed arrow in illustratively depicts the linear movement of the movable section 132 alternately toward and away from the capillary 124 and the fixed section 128 .
[0052] The one or more fixed segments 128 and the one or more movable segments 132 can be configured as a mostly solid body of material in general. Depending on the embodiment, the one or more fixed segments 128 and the one or more movable segments 132 can include various features disposed on, in, or disposed (formed, designed, added, etc.) through their bodies, such as for holding or conducting liquids or gels, supporting or guiding capillaries, accommodating or defining a path for light transmission, mounting to a device support, engaging an actuator, communicating with a circuit system, providing identification or other information of the capillary array holder 120, etc.
[0053] The one or more flexible sections 136 are configured to enable the one or more movable sections 132 to move relative to the capillary 124 and the one or more fixed sections 128, in particular to translate linearly along the device axis. To this end, the one or more flexible sections 136 are configured to flex (or deform, expand, etc.) in response to the movement of the one or more movable sections 132. Depending on the configuration, such "flexing" may involve movement of one or more parts of the one or more flexible sections 136 in one or more directions and 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 fixed section 128). In other words, the movable section 132 (or both the movable section 132 and the fixed section 128) is "rigid" relative to the flexible section 136. The flexible section 136 is "flexible" in the sense that it is more flexible or compliant (or weaker) than the fixed 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 fixed section 128, while the movable section 132 will not flex, but will move toward (in its direction) the flexible section 132 and transfer all or most of the applied force to the flexible section 132.
[0054] In some embodiments of the flexible configuration, the flexible section 136 may have an "open frame" configuration (in Figure 1A-1F136). Such an open frame configuration may be a major contributing factor to the flexibility of the flexible segment 136, as compared to the inherent flexibility of the solid material of the flexible segment 136. In the case of an open frame configuration, the three-dimensional space occupied by the flexible segment 136 may be primarily open space rather than solid material, particularly compared to the fixed segment 128 and the movable segment 132. Most of the three-dimensional space occupied by the fixed segment 128 and the movable segment 132 is solid material, which makes the fixed segment 128 and the movable segment 132 structurally more rigid (less flexible and less compliant) and stronger or more robust than the flexible segment 136, and therefore more resistant to deformation (and less responsive to applied forces). In contrast, a large percentage of the three-dimensional space occupied by the flexible segment 136 is open space. As examples of "primarily open space" or "a large percentage of open space", the percentage of the three-dimensional space occupied by the flexible segment 136 that is open space may be greater than 30%, or greater than 50%, or greater than 70%.
[0055] The open frame configuration can be achieved by an open space arrangement (array, pattern, etc.) formed in and / or through the solid portion of the flexible segment 136. In other words, the open frame configuration can be achieved by configuring the body of the flexible segment 136 to define an open space arrangement. For example, the flexible segment 136 can include an arrangement of holes (openings) passing through the solid portion of the flexible segment 136 in one or more directions (x-axis, y-axis, and / or z-axis). The holes can have any size and shape (circular, elliptical, linear, polygonal, diamond-shaped, etc.) to effectively achieve the degree of flexibility required for a given embodiment. The holes can be defined by an arrangement of "thin" structural members or compliant beams (e.g., a mesh, grid, grid, perforated body, etc. formed by 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 fixed segment 128 or the movable segment 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 section 132 (or the additional fixed section 128). As a non-exclusive example, a "thin" structural member may have a width in a plane (e.g., the device plane) that is no greater than 20%, or 40%, or 60% of the length, width, and height of the movable section 132 (or the additional fixed section 128). In conjunction with the following Figures 4A-6B Some examples of open frame configurations of the flexible section 136 are further described. In another example, the holes can be open cells distributed throughout the bulk material of the flexible section 136, such as similar to open cell foam or memory foam (e.g., polyurethane (PU) foam or polyethylene terephthalate (PET) foam).
[0056] Because the open frame configuration (and the flexibility of its structural components) makes the flexible section 136 flexible, in this embodiment, the flexible section 136 can be made of a wide variety of materials, and further can be made of the same material as the fixed section 128 or the movable section 132. Such a configuration allows the capillary array holder 120 (including the fixed section 128, the movable section 132, and the flexible section 136) to be manufactured as a single-piece article using techniques appropriate to the selected materials and 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); polymethyl methacrylate (PMMA); polyetheretherketone (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 can be a two-component polymer mold with a conductive carbon fiber filler segment overmolded with an insulating polymer, thereby creating an integrated high voltage (HV) electrode in a polymer housing.
[0057] In other examples of flexible configurations, the flexible section 136 may not necessarily have an open frame configuration as described above, but may be constructed of a material that is inherently highly flexible. In this case, the fixed section 128 and the movable section 132 may be constructed of different materials that are less flexible than the material of the flexible section 136. In this context, the term "highly flexible" is relative to the flexibility of the fixed section 128 and the movable section 132. For example, in response to an applied (actuation) force, the flexible section 136 will easily flex (move, have compression and / or expansion / extension) due to being highly flexible, while the fixed section 128 and the movable section 132 will not flex (at least not to any significant extent). Examples of highly flexible materials for the flexible section 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.
[0058] In other examples of flexible configurations, the flexible segment 136 may include one or more hinges or other types of components that define a pivot axis. Each hinge may connect two sub-segments of the flexible segment 136, thereby allowing one or both of the sub-segments to pivot about the pivot axis in response to a force. For example, Figure 1A-Figure 1C The illustrated flexible section 136 may include one or more hinges having a pivot axis in the z-direction.
[0059] In other embodiments, the capillary array holder 120 may include an intrinsic actuator. For example, all or part of the movable section 132 and / or the flexible section 136 may be an intrinsic actuator or an intrinsic actuation component (i.e., may be composed of an intrinsic actuation material). Similarly, the movable section 132 and / or the flexible section 136 may include an intrinsic actuation component that is in abutting contact with or coupled to a non-intrinsic actuable component (i.e., a component that is not an intrinsic actuator itself). In other words, in either case, the movable section 132 and / or the flexible section 136 may be or may include an intrinsic actuation component. Typically, an intrinsic actuation material is a material that is capable of reversibly changing its shape (or deformation) 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)). The specific type and material composition of the intrinsic actuation component may be such as now known in the field of "soft" robotics or later developed. Examples of intrinsic actuation components include, but are not limited to, dielectric elastomeric actuators (DEAs), shape memory polymers (SMPs), and shape memory alloys (SMAs).
[0060] DEA can be configured as a compliant plate capacitor, in which a body or block of intrinsically actuated (DEA) material is sandwiched between two planar (plates, layers, films, coatings, etc.) electrodes (or alternatively, two ionic hydrogels, such as polyacrylamide hydrogels). The electrodes are coupled to a high voltage (HV) source, which may be the same as the HV source used for electrophoresis and described herein. In response to the application of a high voltage (i.e., a high voltage electric field) between the electrodes, the DEA material becomes strained such that, in effect, the DEA material is squeezed between the electrodes by electrostatic pressure (i.e., its thickness is reduced) and subsequently expands in a plane parallel to the electrodes. The amount of electrostatic pressure 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 the movable segment 132 and / or the flexible segment 136 is composed of a DEA material, the DEA material and the accompanying electrodes may be positioned and oriented such that the application of a high voltage causes the movable segment 132 and / or the flexible segment 136 to shrink (contract) along the device axis. In another example, if the DEA component is separate from (but in contact with or coupled to) the movable segment 132 and / or the flexible segment 136 (or equivalently, the movable segment 132 and / or the flexible segment 136 include the DEA component as well as the extrinsic actuatable component), the DEA component (DEA material and accompanying electrodes) can be positioned and oriented such that the electric field-induced contraction or shrinkage causes the DEA component to push or pull the movable segment 132 and / or the flexible segment 136 along the device axis. Examples of DEA materials include, but are not limited to, acrylic elastomers (e.g., VHB 4910 elastomer commercially available from 3M, St. Paul, MN, USA), silicones (e.g., PDMS), and natural rubbers (e.g., polyisoprene elastomer or latex).
[0061] In a typical example, the SMP can be pre-strained (pre-stretched) to a deformed shape by applying thermal energy (particularly heating the SMP to a temperature above its glass transition temperature or melt transition temperature), and then cooled to maintain the deformed shape. Subsequently, in response to another application of thermal energy, the deformed SMP will recover back to its original (undeformed) shape as the strain is released. Thus, like the DEA component, if all or a portion of the movable section 132 and / or the flexible section 136 is composed of SMP material, the SMP component can be positioned and oriented so that the application of thermal energy changes the deformed movable section 132 and / or the flexible section 136 back to its or their original shape. Alternatively, if the SMP component is separate from (but in contact with or coupled to) the movable section 132 and / or the flexible section 136 (or equivalently, the movable section 132 and / or the flexible section 136 include the SMP component and the non-intrinsic actuatable component), the SMP component can be positioned and oriented such that the heat-induced shape change causes the SMP component to push or pull the movable section 132 and / or the flexible section 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. As will be appreciated by those skilled in the art, one or more of these polymers may be provided as a block copolymer with one or more other polymers. Another example of a heat-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 substituted with polyhedral oligomeric silsesquioxane (POSS).
[0062] In addition to heat-activated SMPs, the SMP component may alternatively be a light-activated SMP. In this case, the shape of the SMP will deform in response to irradiation with a first wavelength of light (e.g., UV light). Subsequently, the SMP returns to its original shape in response to irradiation with a different second wavelength of light. Examples of light-activated SMP materials include, but are not limited to, cinnamic acid and cinnamylidene acetic acid, and more generally, polymers containing cinnamic acid groups.
[0063] In another example, the SMP component can be an electrically activated SMP. In this case, the shape of the SMP will deform in response to the application of a voltage (electric field) of appropriate magnitude. The electrically activated SMP can be made conductive by including conductive fillers (such as, for example, carbon nanotubes (CNTs), carbon fibers, carbon black, or metal (e.g., nickel Ni) powders) in the polymer material.
[0064] In another example, the SMP component can be a magnetically activated SMP. In this case, the shape of the SMP will deform in response to the application of a magnetic field. The magnetically activated SMP can be made magnetically responsive by including magnetic fillers (such as, for example, magnetite or certain metal (e.g., Ni) particles or fibers) in the polymer material.
[0065] SMA can be deformed when in a cold (unheated) state, and subsequently returned to its original shape by applying thermal energy. As with other shape memory materials, this cycle is reversible. Typically, SMA components are configured to be compliant or spring-like, such as by being formed into 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 composition of the alloy, some of these SMAs may additionally be magnetic SMAs (MSMAs), also known as ferromagnetic SMAs (FSMAs), which are capable of changing shape in response to the application of a magnetic field (as an alternative to heating). Examples of MSMA materials include, but are not limited to, the aforementioned Ni-Mn-Ga based alloys, Ni-Fe-Ga, and Fe-Pd.
[0066] 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 of (or scale of) millimeters (mm), i.e., generally in the range of fractions from 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 from 30 mm to 130 mm.
[0067] In general, any technology suitable for the materials utilized (e.g., organic polymers, metals, metalloids, etc.) and the size of the components can be used to manufacture / produce the capillary array holder 120. The specific manufacturing technology implemented should be highly suitable for forming the flexible section 136 according to the configuration described herein. In general, various technologies used to manufacture miniaturized articles (including technologies utilized in the fields of microfluidics or microelectronics) can be suitable for manufacturing the capillary array device 100. In the case of polymers or plastics, examples of manufacturing technologies include, but are not limited to, microinjection molding and 3D printing. In the case of metals or metalloids, various additive, subtractive and molding manufacturing technologies can be used. Examples of additive technologies include, but are not limited to, 3D printing (e.g., lithography-based metal manufacturing (LMM)), electroplating molding, 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), etc.), wet etching (i.e., chemical etching such as by using hydrofluoric acid or other acids) followed by diffusion bonding, micromachining, micromilling, microlaser machining, and micro-electrodischarge machining (EDM). Examples of forming techniques include, but are not limited to, microstamping, microembossing, and LIGA (German: Lithographie, Galvanoformung, Abformung).
[0068] In a typical (but not exclusive) embodiment, the capillaries 124 are constructed of an optically transparent material. In the context of the present disclosure, an "optically transparent" material is a material that allows transmission of light propagating at a range of wavelengths that includes (at least) the excitation light EX and the emission light EM employed in the use of the capillary array device 100 (described further below, and see Figure 1F) of one or more wavelengths. Depending on the embodiment, the excitation light EX and / or the emission light EM can be ultraviolet light, visible light or infrared light. Examples of materials for the capillary 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 can be coated (i.e., surrounded circumferentially by the coating). The coating can be used to protect the capillary 124 from damage or destruction, and also to block light transmission into and out of the capillary 124. Examples of materials for the coating include, but are not limited to, polyimide (PI), acrylates, silicones, and fluoropolymers. If coated, at least one section of each capillary 124 is bare (uncoated), so that the bare (or exposed, or uncoated) section (referred to as a "capillary window") is exposed to the surrounding environment and thus allows light to transmit into and out of the capillary 124. The capillary 124 can be manufactured by any suitable technique now known or later developed. As an example, the capillary 124 can be manufactured by first forming a tube portion (including a lumen), then coating the entire length of the capillary 124, and then stripping the coating from a segment of the capillary 124 to form a capillary window.
[0069] In the context of the present disclosure, excitation light EX may refer to a beam (or light) directed from a light source external to the capillary array device 100 to the capillary 124 (or to the window of the capillary 124, if provided) so as to thereby illuminate the sample retained in the corresponding capillary 124. Depending on the embodiment, the beam of excitation light EX may or may not be coherent. Such a light source may be part of an analytical instrument configured to perform optical-based measurements of analytes in a sample to determine characteristics or properties (e.g., the concentration of one or more analytes) and / or to obtain microscopic images, etc., as understood by those skilled in the art. Emission 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, the emission light EM may be caused by different types of stimuli (such as chemical reagents), in which case excitation light EX may not be required.
[0070] In some examples, the excitation light EX can 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 can be used to "excite" the target analyte in the sample in the capillary 124 by inducing fluorescence (e.g., from an intrinsic fluorescent analyte, or from a fluorophore added or bound to the analyte, etc.) or similar phosphorescence. For convenience, the term "excitation" is used herein to refer to all such cases, including illumination that does not involve fluorescence or phosphorescence. In the example of acquiring an image, the emission light EM is light emitted from the capillary 124 within the field of view of the camera, and the light is processed as needed to construct an image of the sample in the capillary illuminated by the excitation light EX. In the example of measuring absorbance (or transmittance), the emission light EM emitted from the capillary 124 is attenuated due to partial absorption of the excitation light EX by the sample in the capillary 124. In this case, the emission light EM can have the same wavelength as the excitation light EX, but can have a lower intensity. In the example of measuring fluorescence, the emission light EM is the light emitted from the analyte in response to the wavelength of the excitation light EX. In this case, the emission light EM has a different wavelength than the excitation light EX. Another example is fluorescence microscopy, where the captured image is based in part on the fluorescence emission. For convenience, the term "emission" is used herein to refer to all such cases, including non-fluorescent transmission.
[0071] In a typical (but not exclusive) example, the axial length of the capillary 124 is in the order of millimeters (as defined above), and the outer diameter of the capillary 124 is in the order of micrometers (μm), that is, typically from 1 μm to a fraction of 1000 μm (1 mm). In an example, the length of the capillary 124 is in the range of 20 mm to 120 mm. In an example, the outer diameter of the capillary 124 is 80 μm to 200 μm (e.g., a hollow fused silica tube without a protective sleeve), or 150 μm to 900 μm (e.g., a fused silica core with a protective sleeve), with a specific example of 80 μm. The capillaries 124 are arranged side by side along the transverse axis, typically with uniform spacing. In one example, the spacing between adjacent capillaries 124 along the transverse axis is in the range of 1 mm to 10 mm. In another example, the capillaries 124 can be spaced apart in a more compact package, but crosstalk effects may cause problems with increased background and ghost peaks. Concepts for mitigating these negative effects while allowing for more compact packaging are described in International Application No. PCT / US2021 / 044806, filed on August 5, 2021, and entitled "CAPILLARY ARRAY WINDOWHOLDER AND RELATED SYSTEMS AND METHODS," the entire contents of which are incorporated herein by reference. In examples where the capillary 124 includes a capillary window, the axial length of the capillary window ranges from 500 μm to 4 mm (4000 μm).
[0072] exist Figure 1A In the example shown, the capillary array holder 120 includes a fixed section 128, a movable section 132, and a flexible section (or flexible connector) 136 between the fixed section 128 and the movable section 132 relative to the device axis. The capillary 124 can be configured as a detection cell to accommodate a sample detected / measured by an associated analytical instrument. In some embodiments, the sample flows through the capillary 124 in a direction along the device axis during the optical detection / measurement step, in which case the capillary 124 serves as a flow cell. For these purposes, the capillary array holder 120 may include a detection region 140 that extends through the height (thickness) of the capillary array holder 120 (i.e., from the top surface 144 to the bottom surface 148 ( Figure 1D )). The detection region 140 is configured to allow the emission light EM to be transmitted out of the detection region 140, or to allow the excitation light to be transmitted into the detection region 140 (see Figure 1F). If the capillary 124 is coated and provided with a window as described above, the capillary 124 is mounted to the capillary array holder 120 such that the detection region 140 spans the length (at least a majority) of the overlying window. In some embodiments, the detection region 140 is part of the fixed section 128, which can facilitate ensuring optical alignment of the detection region 140 with the optical system of the analytical instrument. Alternatively, the detection region 140 can be part of the movable section 132.
[0073] The capillary array device 100 can be mounted to any suitable analytical instrument that is configured to perform optical-based measurements on an analyte contained in the capillary 124. Depending on the embodiment, the capillary array device 100 can be loaded directly into a housing or console of the analytical instrument and positioned to align with the optical system of the analytical instrument, or can be configured as part of an assembly or cartridge loaded into a housing or console. For example, the capillary array holder 120 can include one or more mounting features configured to engage a device support that is in turn configured to engage a receiver of the analytical instrument, particularly to properly optically align the capillary 124 with the optical system of the analytical instrument, etc.
[0074] In some embodiments, the capillary array device 100 integrally includes a container. Depending on the embodiment, some containers can be used as a source of liquid and / or gel to be loaded (introduced or injected) into the capillary 124, while other containers can be used as receivers for receiving liquid and / or gel leaving the capillary. As an example, the liquid can be a solution containing a sample, a buffer solution, a reagent, a liquid containing a marker (e.g., a dye, a fluorophore, etc.), etc.; and the gel can be a separation medium formulated for electrophoresis or chromatography. The container can be formed in the top surface 144 (i.e., the top surface of the fixed section 128 and / or the movable section 132) of the capillary array holder 120. Examples of containers include holes and slots.
[0075] In the illustrated example, the movable section 132 includes a linear (one-dimensional) array of holes 148, which are positioned (spaced apart along the transverse axis) so that each capillary 124 is aligned with a corresponding one of the holes 148 along the device axis. The movable section 132 also includes a first slot 152 extending along the transverse axis. In addition, the fixed section 128 includes a second slot 156 extending along the transverse axis. The first slot 152 and the second slot 156 have a width greater than the transverse distance spanned by the array of capillaries 124. In this way, the first slot 152 and the second slot 156 are wide enough along the transverse axis to receive all of the capillaries 124 at the same time. The holes 148 can be used to accommodate separate samples or other liquids that are not expected to be mixed or cross-contaminated, thereby facilitating the analysis of samples in the corresponding capillaries 124 separately. Movement of liquid or gel between adjacent wells 148 is limited (and preferably completely prevented) due to the geometry of the dedicated capillaries / grooves / wells (i.e., well-separated channels) and also due to surface tension, particularly in small-scale or miniaturized configurations where surface tension can play a significant role in the fluid dynamics of the capillary array device 100. Grooves 152 and 156 may be used to supply the same liquid or gel to all capillaries 124, or to receive the output of all capillaries 124 when such outputs do not need to remain separate from one another.
[0076] In the example shown, the capillary 124 is responsive to movement of the movable section 132 (from Figure 1A 148 is movable in and out of the corresponding hole 148 (moving to the left in the perspective of the movable section 132). The capillary 124 can be further moved into and out of the first slot 152 in response to further movement of the movable section 132 (further moving to the left). More specifically, each capillary 124 has a first capillary end 160 and an axially opposite second capillary end 164. The first capillary end 160 can be moved into and out of the corresponding hole 148 and the first slot 152. In this example, the hole 148 is positioned closer to the capillary 124 than the first slot 152. Therefore, when the movable section 132 moves toward the capillary 124 (to the left), the first capillary end 160 will first approach the hole 148 before approaching the first slot 152. Also in this example, the second slot 156 is positioned relative to the fixed position of the capillary 124 so that the second capillary end 164 is permanently disposed in the second slot 156.
[0077] In other embodiments, second slot 156 can be located on a movable section of capillary array holder 120, which can be in addition to the illustrated movable section 132. In other embodiments, movable section 132 (and / or additional movable section(s)) can include additional holes and / or slots, depending on the application.
[0078] In this example, Figure 1A The capillary array device 100 in the first (or initial) position is shown. At the first position, the movable section 132 has not been moved (e.g., actuated), and therefore the flexible section 136 is relaxed (without deflection). The first position can also correspond to a storage 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 can also correspond to a capillary loading position. In other words, liquid or gel can be dispensed into the second groove 156. The liquid or gel is then loaded into the capillary 124 via the second capillary end 164. In this example, the liquid or gel can be passively loaded into the capillary 124 by capillary action (or wicking), as understood by those skilled in the art. Depending on the amount dispensed into the second groove 156 and the time period assigned for loading, the lumen (inner pore) of the capillary 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 moving device (e.g., a positive displacement pump such as a syringe or vacuum pump) to load the capillaries 124 with liquids or gels. However, in some applications, loading of certain liquids or gels can be accomplished electrokinetically, as described below.
[0079] Figure 1B 1 and 2. Capillary array device 100 is shown in a second position. Capillary array device 100 has been moved from the first position to the second position by moving (e.g., actuating) movable section 132, as shown by Figure 1B The movement of the movable section 132 causes the flexible section 136 to flex. By way of example, Figure 1B 136) and outward extension or bulging of the flexible section 136 in either direction along the transverse axis, as indicated by Figure 1B The various portions or structural members of the flexible section 128 may move in various directions as part of the flexural response, in which case, Figure 1B The outward lateral direction shown can be the primary direction of flexure or movement. The flexure 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, the flexure of the flexible section 136 reduces the overall axial length of the capillary array holder 120.
[0080] In the second position, the movable section 132 has moved (translated linearly along the device axis) far enough (in Figure 1B148). The capillary end 160 is moved to the left in the hole 148 so that the first capillary end 160 is now disposed in the corresponding hole 148. Depending on the embodiment, the moving distance required for the first capillary end 160 to reach the hole 148 may be different. As a non-limiting example, the distance may be more than ten or tens of millimeters, or only a few millimeters (e.g., 2-5 mm). At the second position, any liquid or gel contained in the hole 148 may be passively loaded into the capillary 124 through the first capillary end 160 by capillary action. The liquid or gel may be dispensed into the hole 148 before the first capillary end 160 moves into the hole 148, in which case the liquid or gel will be sucked into the capillary 124 when the first capillary end 160 is moved into the hole 148. Alternatively, the liquid or gel may be dispensed into the hole 148 after the first capillary end 160 moves into the hole 148, in which case the liquid or gel will be sucked into the capillary 124 when the liquid or gel is dispensed into the hole 148. Depending on the application, in the second position, the second groove 156 can serve as a receiver for collecting any liquid or gel exiting the second capillary end 164 .
[0081] Figure 1C 1 and 2. Capillary array device 100 is shown in a third position. Capillary array device 100 has been moved from the second position to the third position by further moving (eg, actuating) movable section 132, as shown by Figure 1C That is, the movable section 132 has been further linearly translated along the device axis, which in this example means that Figure 1B This further movement causes the flexible section 136 to bend further, as indicated by Figure 1C , and causes the overall axial length of the capillary array holder 120 to be further shortened. In the third position, the movable section 132 has moved far enough (beyond the hole 148) that the first capillary end 160 is now disposed in the first groove 152. As in the second position, if the first groove 152 contains a liquid or gel, the liquid or gel can now be passively loaded into the capillary 124 through the first capillary end 160 by capillary action. Alternatively, depending on the application, in the third position, the first groove 152 can be used as a receiver for collecting any liquid or gel that leaves the first capillary end 160.
[0082] Figure 1A-Figure 1CThe states of the flexible section 136 in the first position, the second position, and the third position are depicted in a schematic manner, respectively. The exact type of response of the flexible section 136 to the movement of the movable section 132 depends on the specific configuration of the flexible section 136. As described above and further below, many different configurations of the flexible section 136 are possible and are covered by the present disclosure. Figure 1A-Figure 1C In the drawings, the lines delineating the boundaries of the flexible section 136 do not necessarily represent continuous or solid walls or edges. Alternatively, depending on the flexible configuration, these lines may represent the outer envelope of the three-dimensional space occupied by the flexible section 136 at the first position, the second position, and the third position.
[0083] In some examples, all or a portion of the flexible section 136 is configured as a compliant spring that applies a force directed toward the movable section 132 (i.e., in accordance with the translation of the movable section 132 from the first position (in ... Figure 1A-Figure 1C Thus, in the absence of a force applied to movable section 132, flexible section 136 can bias capillary array device 100 to the right. Figure 1A In this case, when it is desired to move the movable section 132 to Figure 1B The second position shown or Figure 1C When the movable section 132 is in the third position shown, the force applied to the movable section 132 will be large enough to overcome the biasing force of the flexible section 136. Once the second position or the third position is no longer desired, the force applied to the movable section 132 can be removed. Thus, the biasing force moves the movable section 132 back to the first position (i.e., the nominal or default position) without actively pushing or pulling the movable section 132 back to the first position.
[0084] The specific use and movement sequence of the capillary array device 100 depends on the specific application in which the capillary array device 100 is being utilized. One or more of the first position, the second position, and the third position may be utilized one or more times during one or more time periods during the use of the capillary array device 100. Also during one or more time periods during the use of the capillary array device 100, optical measurements of samples in the capillaries 124 may be performed by an appropriate analytical instrument in which / on which the capillary array device 100 is mounted or installed, as will be understood by those skilled in the art. Such measurements may involve the transmission of light from a detection region 140 equipped with the capillary array holder 120, or the transmission of light to and from the detection region.
[0085] In general, liquid or gel can be distributed (supplied or delivered) into hole 148, first groove 152 and second groove 156 by any suitable technique, which can be manual or automatic. For example, a user can manually distribute liquid or gel by using an appropriate dispensing device (such as a pipette, syringe, etc.). As another example, capillary array device 100 can be loaded into an instrument with an automated liquid / gel processing system, as understood by those skilled in the art. In such a system, a reservoir (e.g., a bottle) containing a supply of liquid or gel can be connected to a liquid / gel line, which in turn is connected to one or more pumps and a dispensing device, which can be moved in an automatic manner, such as a motor-driven pipette head. However, the ability to manually supply liquid and gel to capillary array device 100 can be considered advantageous in many applications because it avoids the need for an automated liquid / gel processing system.
[0086] Capillary array device 100 can be provided as a "consumable" article, for example, as a single-use device. That is, capillary array device 100 can be disposable after use. For example, capillary array device 100 can be used to load a sample into capillary 124 once and then perform a single analysis run on these samples. In other words, capillary array device 100 can be used for a single iteration of capillary loading and analysis run steps. Thereafter, capillary array device 100 can be discarded, and a new (fresh) capillary array device 100 can be used to perform additional analysis runs on additional samples. The consumable aspect or disposability of capillary array device 100 eliminates the requirement for cleaning, rinsing, washing or purification of capillary array device 100, and eliminates any risk of cross contamination of capillary array device 100 between separate different analysis runs.
[0087] Figure 1D 1 is a longitudinal side elevation view (along the device axis) of a capillary array device 100 according to an embodiment, the capillary array device being shown coupled to an actuator (assembly) 168. Actuator 168 may include an actuating device (or stimulator or activator) 172 of a known type (such as a stepper motor, solenoid, etc.) and a mechanical link 176 (e.g., an actuator arm, a plunger, etc.) coupled to actuating device 172. Actuating device 172 is configured to linearly translate mechanical link 176 along the device axis, such as Figure 1D. The movable section 132 may include one or more features configured to be coupled to, engaged with, or at least contacted by the actuator 168 (or more specifically, the mechanical link 176). In the example shown, the movable section 132 (e.g., on its underside) includes or is attached or mounted to a table or platform 180 that is configured to be coupled to or contacted by the mechanical link 176. In another example, an axial end surface 184 of the movable section 132 is configured to be coupled to or contacted by the mechanical link 176. As will be appreciated by those skilled in the art, any suitable coupling arrangement may be provided to create a mechanical coupling between the movable section 132 and the mechanical link 176. Examples of connection arrangements include, but are not limited to, a snap-fit arrangement (e.g., the mechanical link 176 snaps into a recess in the movable section 132), an abutment arrangement (e.g., respective surfaces of the movable section 132 and the mechanical link 176 engage so that the mechanical link 176 can push the movable section 132 toward the flexible section 136, or if the flexible section 136 is not spring biased, otherwise pull the movable section 132 back away from the flexible section 136), a fastening arrangement (e.g., using fastening components such as clamps, spring clips, threads, etc.), a magnetic connection arrangement (e.g., the movable section 132 and the mechanical link 176 include magnets oriented to attract each other), and the like.
[0088] In another example, the movable section 132 and the mechanical link 176 can be connected in a non-contact manner. For example, the movable section 132 and the mechanical link 176 (or the actuator 172 itself, in the absence of the mechanical link 176) may include magnets oriented to repel each other, so that the movement of the mechanical link 176 toward the movable section 132 repels the movable section 132 toward the flexible section 136. In this context, a "magnet" can be a permanent magnet or an electromagnet. If at least one of the magnets (of the movable section 132, or of the mechanical link 176 or the actuator 172) is an electromagnet, the magnetic field can be controlled by the current supplied to the electromagnet. In this case, the mechanical link 176 may not be required, or at least the mechanical link 176 may not be required to move toward and away from the movable section 132.
[0089] In another example, the actuation may be performed manually by the user. In this case, Figure 1D One or more of elements 172, 176, and 180 in FIG. 1 may represent levers, handles, or other components that are manipulated by a user.
[0090] In just combined Figure 1DIn the described examples, actuator 168 may be referred to as an extrinsic actuator to distinguish it from the intrinsic actuators described earlier in this disclosure. Extrinsic actuators typically rely on physical (or mechanical) contact between an actuating device (or stimulator or activator) 172 and the movable section 132, in conjunction with some type of mechanical link 176 just described. Thus, extrinsic actuators are typically "contact" actuators, with at least one exception being the above-mentioned example of utilizing repelling magnets. In other examples, actuator 168 may be an intrinsic actuator, in which at least a portion of the movable section 132 and / or the flexible section 136 is considered to include an intrinsic actuating component, as described earlier in this disclosure. When the actuator 168 is configured as an intrinsic actuator, the actuator (or stimulator or activator) 172 can be a voltage source (e.g., as part of a circuit system), a heat source (e.g., a resistive heating device that produces Joule (Ohm) heating), a light source (e.g., a lamp configured to emit electromagnetic energy of an appropriate wavelength, a light emitting diode (LED), a laser, a laser diode (LD), etc.), or a magnetic source (e.g., one or more magnets). In the case where an intrinsic actuator is provided, the link (or connection) between the actuator 172 and the intrinsic actuator can be an electrical interconnection (wiring and electrodes) or a "non-contact" (or wireless) link, such as heat or electromagnetic energy (e.g., a light beam) propagated through the air, or a magnetic field.
[0091] Figure 1E1 is a longitudinal side elevation view of a capillary array device 100 according to the present disclosure, the capillary array device being shown coupled to an electrical circuit. 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 an electrode 192 positioned in one or more of the hole 148, the first slot 152, and the second slot 156. The electrode 192 may be placed in electrical communication with the HV source 188 (and any associated circuitry) via appropriate electrical interconnects, such as electrical wiring; electrical contacts; liquid-tight electrical feedthroughs or "through holes" formed through the body of the capillary array holder 120 below or to the sides of the hole 148, the first slot 152, and / or the second slot 156, etc., as understood by those skilled in the art. The electrode 192 may be provided and electrically coupled to the HV source 188 as desired for a given application. Specifically, the electrical configuration can be used to apply a voltage (potential difference) across the length of the capillary 124 (between the first axial end 160 and the second axial end 164). For example, the electrode 192 located in the hole 148 and / or the first groove 152 can be used as an anode, and the electrode 192 located in the second groove 156 can be used as a cathode. The applied voltage can be used to assist in loading the liquid into the capillary 124 and / or transporting the liquid through the capillary 124 by electrodynamic force. In some examples, the applied voltage is used as part of electrophoresis (specifically, capillary electrophoresis or CE) of the sample in the capillary 124, as described elsewhere herein. As an example, the applied voltage can be in the range of from 0.2 kV to 5 kV.
[0092] In an example, one or more of the electrodes 192 can also be used to generate an electric field that excites (activates) an electrically-active intrinsic actuator, as described above.
[0093] exist Figure 1E In an embodiment of the present invention, the holes 148 do not need to be connected to the HV source 188 together, but the holes 148 can be individually addressed by the HV source 188. For example, an appropriate switch 196 can be set in the circuit system between the HV source 188 and each electrode 192 in the corresponding hole 148. With this configuration, voltage can be selectively applied to any one or more of the capillaries 124, and the voltage can be applied according to a predetermined sequence required by the method scheme. In addition, voltage can be applied to one or more selected capillaries 124 once or multiple times according to one or more predetermined pulse widths, one or more pulse shapes, and pulse sequences.
[0094] Figure 1F1 is a longitudinal side elevation view of a capillary array device 100 according to an embodiment of the present disclosure, the capillary array device being shown coupled to an optics-based measurement device (or system) 106. The optics-based measurement device 106 can be configured and function according to any technology (now known or later developed) suitable for analyzing samples in the capillary 124. In a typical example, the optics-based measurement device 106 includes a light source 110 and a light detector (or camera) 114. The light source 110 (and any associated excitation optics required) is configured to generate an excitation beam EX and direct it to a portion of the capillary 124 located at a detection region 160 (which can be a capillary window as described above). The light detector or camera 114 (and any associated emission optics required) is configured to receive or capture an emission beam EM emitted from a portion of the capillary 124 located at the detection region 160. As shown, both sample excitation and detection can be performed on the same side of the capillary array device 100 (such as the top side shown). Alternatively, the optics-based measurement device 106 can be configured for through illumination, by which sample excitation and detection are performed on opposite sides of the capillary array device 100 (e.g., the light source 110 can be positioned above the capillary array device 100, and the light detector or camera 114 can be positioned below the capillary array device, or vice versa). If desired, a suitably configured light trap (or "beam dump") 118 can be positioned to capture or absorb stray excitation light and / or emission light. In some applications, excitation or stimulation of the sample can be accomplished 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.
[0095] In an embodiment, the capillary array device 100 is configured for capillary electrophoresis (CE), that is, configured to perform a CE run on a sample in the capillary 124. In this case, and Figure 1A-1F In the example shown, hole 148 can be used as a sample hole, which is configured to accommodate a separate sample (e.g., sample solution volume), and it is expected that the sample is analyzed and separated by CE. The first groove 152 can be used as a buffer tank configured to accommodate an appropriate buffer solution. The buffer solution is used as an electrolytic solution that can conduct electric charge (i.e., as an ion source), and can be configured to perform other functions such as pH control. The second groove 156 can be used as a gel tank configured to accommodate a CE separation medium, which is generally provided in the form of a polymer gel that can be solid but porous. The specific type and composition of the CE separation medium depends on the type of analyte to be separated, as understood by those skilled in the art. Examples of CE separation media include, but are not limited to, polyacrylamide, agarose, and certain starches.
[0096] 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 described above and in Figure 1A-1F According to the method, the capillary array device 100 is initially arranged in Figure 1A The first position shown in the figure, which can be referred to as the gel loading position. The second groove 156 (gel groove) is filled with a desired amount of CE separation medium. The amount of CE separation medium allocated to the second groove 156 can depend on the specific method scheme being implemented, which in turn can depend on the number and length of the capillary 124 and whether the capillary 124 is completely or partially filled. Next, because the second capillary end 164 is already positioned in the second groove 156, the CE separation medium is passively loaded (or sucked) into the capillary 124 by capillary action. Before or after the CE separation medium is loaded into the capillary 124, the hole 148 (sample hole) is filled with a separate sample (the samples can be the same or different in composition), and the first groove 152 (buffer groove) is filled with a buffer solution.
[0097] Next, the capillary array device 100 moves to Figure 1B The second position shown, which may be referred to as the sample injection position. Specifically, the movable section 132 is actuated to move relative to the (fixed) capillary 124 and the fixed section 128 in the direction of the flexible section 136 until the first capillary end 160 enters the hole 148. With the first capillary end 160 now positioned in the hole 148, the sample is then loaded into the capillary 124. At the second position, due to the electrolyte properties of the liquid and gel in the capillary 124, the sample injection with the HV source 188 ( Figure 1E ) and the circuit of the electrode 192 of the hole 148 and the second groove 156. Therefore, a voltage can now be applied across the length of the capillary 124. Specifically, when the sample is inserted into the front region of the capillary 124, a voltage pulse can be applied to electrodynamically inject the sample. In some examples, this electrodynamic assistance may be required due to the flow resistance presented by the gel phase CE separation medium retained in the capillary 124.
[0098] Next, the capillary array device 100 moves to Figure 1C14 and 152. The third position shown in FIG. 14 is a third position, which may be referred to as the CE operating position. Specifically, the movable section 132 is actuated to further move relative to the (fixed) capillary 124 and the fixed section 128 in the direction of the flexible section 136. During this movement, the first capillary end 160 passes through the hole 148 and enters the first groove 152. At the third position, due to the electrolyte properties of the liquid and gel in the capillary 124, the first groove 152 and the second groove 156, the HV source 188 ( Figure 1E ) and the circuit of the electrodes 192 of the first slot 152 and the second slot 156. A voltage is then applied to the capillaries 124 according to predetermined operating parameters (e.g., amplitude (constant and / or variable or ramped); total duration of the applied voltage; pulse width, pulse shape (e.g., square, triangle, sinusoidal, etc.), and pulse sequence (including pulse frequency)), which are effective for causing electrophoretic separation of different analytes of the sample in each capillary 124 in a manner understood by those skilled in the art. In short, in each capillary 124, the different analytes of the sample migrate through the CE separation medium at different speeds under the influence of the applied voltage and thereby become separated from each other along the length of the capillary 124. The analytes can then be separated from each other by the optical device-based measurement device 106 ( Figure 1F ) The separated analytes in each capillary 124 are detected / measured at the detection region 140. Subsequently, after acquiring CE data from the sample, the capillary array device 100 can be discarded in some embodiments, as described above.
[0099] The present disclosure also encompasses a sample analysis system (or apparatus, analytical instrument, etc.) comprising an actuator and / or a HV source (and associated circuitry) and / or an optically based measurement device, such as described above and correspondingly in Figure 1D , Figure 1E and Figure 1F, an actuator 168, a HV source 188, and an optical device-based measuring device 106 are shown in FIG. In an embodiment, the actuator 168, the HV source 188, and the optical device-based measuring device 106 can be integrated in a housing or a console of a sample analysis system. The sample analysis system may or may not be portable. In practice, the capillary array device 100 can be installed or mounted in or on a sample analysis system. Depending on the application or embodiment, such installation may involve one or more of the following: mounting the fixed section 128 in a fixed position in which the capillary array device 100 (particularly the detection area 140) is properly aligned with the optical device of the optical device-based measuring device 106; coupling the electrode 192 to the HV source 188; and coupling the movable section 132 to the actuator 168. As described above, in some embodiments, any liquids (including samples) and gels to be utilized can be dispensed into wells 148 and / or grooves 152 and 156 prior to installing capillary array device 100 in a sample analysis system. In such cases, there is no need to couple a fluidic device or circuit (whether or not provided by the sample analysis system) to capillary array device 100.
[0100] Figure 22 is an exploded view of an example of a capillary array device 100 and a device support 200 according to an embodiment, the device support being configured to securely support the capillary array device during operation of the capillary array device 100. For simplicity, the capillary 124 is not shown. As an example, the capillary array device 100 can first be mounted to the device support 200 from outside the sample analysis system as described herein, and then the assembly of the capillary array device 100 and the device support 200 can be installed in the sample analysis system. As another example, the device support 200 can be a fixed component of a receiver of the sample analysis system that receives the capillary array device 100, in which case the capillary array device 100 can be mounted to the device support 200 during or after loading the capillary array device 100 into the receiver. In the illustrated example, the body of the device support 200 includes a top surface 222 in which one or more alignment holes (or mounting holes) 226 are formed, which can be blind holes or through holes. The capillary array device 100 includes one or more alignment posts (or pins, etc.) 230 suspended downwardly from the underside of the fixing section 128. The number and positional arrangement (pattern) of the alignment posts 230 match the number and positional arrangement of the alignment holes 226. The capillary array device 100 is mounted 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 has been mounted to the device support 200 and positioned in the receiver of the sample analysis system, the detection area of the capillary array device 100 is aligned with the optical device-based measurement device 106 ( Figure 1F ) are properly optically aligned.
[0101] In another example, the capillary array device 100 may include an alignment hole 226, and the device support 200 may include an alignment post 230. The alignment hole 226 and the alignment post 230 may have any circular or polygonal shape. In another example, the alignment hole 226 and the alignment post 230 may be elongated in at least one dimension (e.g., in the x-direction or the y-direction). For example, the alignment hole 226 may be shaped as a slot, and the alignment post 230 may be shaped as a plate or a tab.
[0102] In an example, the device support 200 may include an actuator opening 234 formed through its thickness (height) that is configured to receive the actuator 168 ( Figure 1D ) of one or more components. In one example, the device support 200 and the actuator 168 can be attached together as an assembly.
[0103] In an example, the device support 200 may include one or more linear guide slots 238 formed in its top surface 232, and the capillary array device 100 may include one or more linear guide rails 242 suspended downwardly from the underside of the movable section 132. The number and position arrangement (pattern) of the linear guide rails 242 matches the number and position arrangement of the linear guide slots 238. Therefore, when the capillary array device 100 is mounted to 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 can assist in maintaining the linearity (straightness) of the movement of the movable section 132 along the device axis. Alternatively, the capillary array device 100 may include the linear guide slots 238, and the device support 200 may include the linear guide rails 242.
[0104] Figure 3 is a longitudinal side elevation view of another example of a capillary array device 300 according to another embodiment of the present disclosure. Figure 3 The capillary array device 300 is shown in a flexed position, for example corresponding to Figure 1B and Figure 1C The capillary array device 300 includes a flexible section 336 configured to be in combination with the above Figure 1A-Figure 1C The capillary array device 100 described herein has a different flexible section 136. Figure 3 In response to the axial movement of the movable section 132 (as indicated by Figure 3 ) and the resulting axial compression of the flexible segment 336, which is configured to flex and move primarily in a downward direction (along the vertical axis, away from the overlying capillary 124), as indicated by Figure 3 In one example, and as described above, flexible section 336 can include one or more hinges (not shown) that facilitate this type of flexure (e.g., hinges that pivot about the y-axis). In many other aspects, the configuration of capillary array device 200 can be the same as described above and in Figure 1A-1F The configuration of the capillary array device 100 shown in FIG.
[0105] Figure 4A-4G An example of a capillary array device 400 according to another embodiment is shown. Figure 4A and Figure 4BCorrespondingly, are a top perspective view and a top plan view of the capillary array device 400. The capillary array device 400 includes a flexible segment 436 having an open frame configuration as generally described above. Specifically, in the present example, the flexible segment 436 is configured as a series of rhombus-shaped flexible segments 446 arranged axially. Depending on their relative positions, each flexible segment 446 can be integrally adjacent to two adjacent flexible segments 446, or adjacent to an adjacent flexible segment 446 and a fixed segment 128, or adjacent to an adjacent flexible segment 446 and a movable segment 132. The flexible segments 446 are defined by a mesh of fine structural members (or compliant beams) 450 (described above), which in turn define rhombus-shaped openings 454 ( Figure 4B ). The flexible segments 446, and therefore the flexible segment 436 as a whole, act as compliant springs that respond to movement of the movable segment 132 in the manner described earlier in this disclosure. Movement of the movable segment 132 axially compresses the flexible segments 446, whereby their diamond shape "flattens," and the flexible segments 446 may also move outwardly along the transverse axis.
[0106] In the present example, the capillary array device 400 also includes one or more structural braces 458, which are configured to stabilize the linear translation of the movable section 132 and / or to facilitate the flexibility and spring action of the flexible section 436. The braces 458 may or may not be considered as part of the flexible section 436, depending on the example. For example, the braces 458 may be considered as a thin structural member 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 flexible section 446 relative to the transverse axis. Each brace 458 is attached to or integral with the fixed section 128 at one end and attached to or integral with the movable section 132 at the other end. In the illustrated example, the braces 458 are shaped as strips, which may have larger dimensions at their ends adjacent to the fixed section 128 and the movable section 132, thereby improving the stability of the configuration. The brace 458 can have a curved shape, as shown. In this example, in response to the movement of the movable section 132 toward the flexible section 436, the brace 458 moves or bulges outward along the transverse axis.
[0107] In many other aspects, the configuration of the capillary array device 400 can be the same as described above and in Figure 1A-Figure 1C. For example, capillary 124 can be fixed to and positioned on a capillary array holder of capillary array device 400 in a manner that is the same as or similar to the configuration of capillary array device 100. Thus, capillary 124 can be fixed to fixed section 128 so that second capillary end 164 is permanently disposed in second groove 156, and first capillary end 160 can be selectively movable into hole 148 and first groove 152 in response to movement of movable section 132. In addition, capillary array device 400 can be combined with the above-described capillary array device 100. Figure 1D-1F The components of the sample analysis system described are used in combination.
[0108] In the present example, the top surface (or the top surface section between the openings) of the capillary array holder (fixed section 128 and movable section 132) includes a plurality of grooves 462 in which the capillary 124 is mounted. At least some of the grooves 462 of the fixed section 128 can be used as fixing sites 466 where the capillary 124 is fixed to the fixed section 128. As a non-exclusive example, a suitable glue can be applied at the fixing sites 466. The grooves 462 of the movable section 132 can assist in guiding the linear movement of the movable section 132 relative to the capillary 124.
[0109] Figure 4C It is along Figure 4B A cutaway perspective top view of the capillary array device 400 is shown taken along line AA, which coincides with one of the capillaries 124 and the associated groove 462 . Figure 4D It is along Figure 4B The cut-away longitudinal side elevation view taken along the same line AA is shown, thus showing the same capillary 124 and associated groove 462. In the present example, some sections of the groove 462 (such as at the entrance to the hole 148 and the first slot 152) may include a tapered or conical portion 470 to assist in guiding the capillary 124 as it enters an open space (such as the hole 148 and the first slot 152) during movement of the movable section 132.
[0110] Figure 4E-Figure 4G 4 is a top plan view of capillary array device 400, which is shown in a first position, a second position, and a third position, respectively. Figure 4E-Figure 4G The flexible section 436 is not shown in FIG. In this example, the capillary array device 400 is combined with the above Figure 1A-Figure 1C The first position, second position, and third position shown describe that the capillary array device 100 operates in the same manner in the first position, the second position, and the third position.
[0111] Figure 5A and Figure 5B An example of a capillary array device 500 according to another embodiment is shown. Specifically, Figure 5A is a top perspective view of capillary array device 500, and Figure 5B FIG. 5 is a top plan view of the capillary array device 500. Figure 5A and Figure 5B 124 is not shown in the capillary array device 500. In this example, the capillary array device 500 includes a guide feature configured to guide the axial movement of the capillary array device 500 to the various operating positions described herein. Such a guide feature can be integrated with the fixed section 528 and the movable section 532 of the capillary array device 500. Specifically as shown, the movable section 532 includes a first axial leg 574 and a first axial recess (or channel, or other axial elongated space) 578, both of which extend along the device axis but on the opposite side of the movable section 532 relative to the transverse axis. The fixed section 528 includes a second axial leg 582 and a second axial recess (or channel, or other axial elongated space) 586, both of which extend along the device axis but on the opposite side of the fixed section 528 relative to the transverse axis. In operation, when the movable 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 (the first axial leg 574, the first axial recess 578, the second axial leg 582, and the second axial recess 586) assist in maintaining the linearity or straightness of the axial movement of the movable section 532 relative to the capillary 124 and the fixed section 528, such as by limiting the lateral movement (along the lateral axis) of the movable section 532. To this end, during the movement of the movable section 532, 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.
[0112] Also, in the present example, the first axial leg 574 may include a first shoulder 590, and the second axial leg 582 may include a second shoulder 594. The first shoulder 590 and the second shoulder 594 may serve as mechanical stops that limit the range of axial movement of the movable segment 532. In other words, if the movable segment 532 moves far enough in the direction of the flexible segment 436, the first shoulder 590 will contact a surface of the fixed segment 528, and / or the second shoulder 594 will contact a surface of the movable segment 532, thereby preventing further axial movement.
[0113] In the example shown, the flexible section 436 of the capillary array device 500 is similar to that described above and in Figure 4A and Figure 4B 4. However, flexible section 436 of capillary array device 500 can have any flexible configuration described and / or illustrated herein.
[0114] In many other aspects, the configuration of the capillary array device 500 can be the same as described above and in Figure 1A-Figure 1C The capillary array device 100 shown in and / or described above and in Figure 4A and Figure 4B The configuration of the capillary array device 400 shown in FIG. 5 is the same or similar. For example, the capillary array device 500 may be configured as described above and in Figure 1A-Figure 1C or Figure 4E-Figure 4G In addition, the capillary array device 500 can be combined with the capillary array device 500 as described above. Figure 1D-1F The components of the sample analysis system described are used in combination.
[0115] Fig. 6A and Figure 6B An example of a capillary array device 600 according to another embodiment is shown. Specifically, Fig. 6A is a top perspective view of capillary array device 600, and Figure 6B 6 is a top plan view of the capillary array device 600. In this example, the capillary array device 600 includes more than one movable segment, namely, a first movable segment 632 and a second movable segment 603. The capillary array device 600 also includes more than one fixed segment, namely, a first fixed segment 628 and a second fixed segment 607 (or equivalently, the fixed segment of the capillary array device 600 includes a first fixed portion 628 and a second fixed portion 607). In the device plane, the first fixed segment 628 is axially positioned between the first movable segment 632 and the second movable segment 603, and the second fixed segment 607 surrounds the first movable segment 632 and the second movable segment 603. In this example, the first fixed segment 628 and the second fixed segment 607 are integrally adjacent, that is, they have a one-piece configuration. However, in other examples, the first fixed segment 628 and the second fixed segment 607 can be separate components.
[0116] In this example, the detection area 140 is located at the first fixed section 628. The hole 148 and the first slot 152 are located at the first movable section 632, and the second slot 156 is located at the second movable section 603. In addition, the capillary array device 600 includes a third slot 611, which is located at the first movable section 632, but can alternatively be located at the second movable section 603, depending on the embodiment. The third slot 611 can be used as an additional liquid or gel source. As in other embodiments, additional slots can be provided for specific applications, if necessary. In this example, the first slot 152 is axially positioned closer to the capillary 124 than the third slot 611 and the hole 148, and the hole 148 is axially positioned farther away from the capillary 124 than the first slot 152 and the third slot 611, and the third slot 611 is therefore axially positioned between the first slot 152 and the capillary 124.
[0117] In the present example, the capillary array device 600 includes a flexible segment 636 that includes a plurality of thin structural members (or compliant beams) 650 separated by openings 654 that pass through the thickness (height) of the flexible segment 636. For example, and as illustrated, one or more structural members 650 interconnect (i.e., are integrally adjacent or attached to) the second fixed segment 607 and one side of the first movable segment 632, and one or more additional structural members 650 interconnect the second fixed segment 607 and the opposite side (“opposite” being relative to the transverse axis) of the first movable segment 632. Similarly, one or more additional structural members 650 interconnect the second fixed segment 607 and one side of the second movable segment 603, and one or more additional structural members 650 interconnect the second fixed segment 607 and the opposite side of the second movable segment 603. In other words, each structural member 650 is tethered to the second fixed section 607 and is also tethered to the first movable section 632 or the second movable section 603. In the present example, the structural member 650 is adjacent to or attached to the inner wall 615 (e.g., the wall 615 facing the central device axis) of the second fixed section 607 and the outer wall of the first movable section 632 or the second movable section 603. As further shown, each of the structural members 650 can include one or more "thick" sections or boxes 619, which can be solid or partially hollow. Each box 619 is larger or "thicker" than the rest of the corresponding structural member 650 (its "thin" section), where the terms "thick" and "thin" are relative to each other. The box 619 can be used to control the flexibility of the structural member 650. For example, a larger (e.g., longer) box 619 can reduce flexibility. Thus, the flexibility of the structural members 650 can be controlled (or adjusted or regulated) by selecting the size of the boxes 619 (and / or the number of boxes 619) provided for each structural member 650. The boxes 619 can also be used to provide the structural members 650 with enhanced structural support.
[0118] In this example, the flexible section 636 is configured such that, in response to the axial movement of the first movable section 632 or the second movable section 603 (as determined by Figure 6B ), the corresponding structural member 650 will pivot (or swing) in the plane of the device, as indicated by the double-headed straight arrow in FIG. Figure 6B The pivot point is located at the interface between the second fixed section 607 and the first movable section 632 and the second movable section 603 .
[0119] In the present example, capillary array device 600 is axially movable between at least three (first, second, and third) positions. Fig. 6A and Figure 6BThe capillary array device 600 is shown in a first (or initial or storage) position. In the first position, the first movable section 632 and the second movable section 603 have not been moved (e.g., actuated), and therefore the flexible section 636 is relaxed (not flexed). In the first position, the first capillary end 160 is positioned inside the first groove 152. Therefore, when a liquid or gel is dispensed into the first groove 152, the liquid or gel will be passively loaded into the capillary 124 via the first capillary end 160 by capillary action. Then, by axially moving the first movable section 632 toward the first fixed section 628 (in Figure 6B The capillary array device 600 can be moved to the second position by axially translating the first movable section 632 to the left in the middle. At the second position, the first capillary end 160 is now positioned inside the third groove 611, which can be filled with a liquid or gel that can be different from the liquid or gel provided in the first groove 152 before or after moving to the second position. Then, by further axially moving the first movable section 632 toward the first fixed section 628 (in the middle), the capillary array device 600 can be moved to the second position. Figure 6B The first movable section 632 is further axially translated to the left in the process, and the second movable section 603 is also axially moved toward the first fixed section 628 (in the process Figure 6B 611). The capillary array device 600 can be moved to a third position by moving the second movable section 603 axially to the right in the middle (in the middle of the capillary array device 600). At the third position, the first capillary end 160 is now positioned inside the hole 148, which can be filled with a liquid or gel that can be different from the liquid or gel provided in the first groove 152 and the third groove 611 before or after moving to the third position. In addition, the second capillary end 164 is now positioned inside the second groove 156, which can be filled with a liquid or gel that can be different from the liquid or gel provided in the hole 148, the first groove 152, and the third groove 611 before or after moving to the third position.
[0120] In another example, the third position can be divided into a third position and a separate fourth position. At the third position, the first capillary end 160 is positioned inside the hole 148. At the subsequent fourth position, the second capillary end 164 is positioned inside the second groove 156. Alternatively, the second capillary end 164 can be positioned inside the second groove 156 at the third position, and then, the first capillary end 160 can be positioned inside the hole 148.
[0121] The specific use, movement sequence and number of different positions of the capillary array device 600 depend on the specific application that is utilizing the capillary array device 600. Therefore, the movement sequence may be different from the movement sequence just described. For example, at the first position, the first capillary end 160 may be initially positioned in any container (e.g., hole 148, first groove 152 and third groove 611) of the first movable section 632, or the first capillary end 160 may not be initially positioned in any of these containers. At other positions (e.g., second position, third position, fourth position, etc.) reached after the first position, the first capillary end 160 may be positioned or may not be positioned in any container of the first movable section 632, and the second capillary end 164 may be positioned or may not be positioned in any container (e.g., second groove 156) of the second movable section 603.
[0122] As in other embodiments, electrodes (such as those described above in conjunction with Figure 1E The described electrode 192) can be included in any of the hole 148, the first groove 152, the second groove 156 and the third groove 611, so as to achieve loading of liquid or gel into the capillary 124 and / or transport of liquid or gel through the capillary 124 by electrodynamics.
[0123] In this example, the flexible section 636 is configured as a compliant spring that causes the first movable section 632 and the second movable section 603 to move toward Fig. 6A and Figure 6B That is, the relaxed state of the flexible section 636 corresponds to the first position. Figure 6B As best seen in , in the relaxed state, the structural member 650 of the flexible section 636 is oriented at an angle relative to the transverse axis (and the device axis). When the first movable section 632 (left) moves toward the first fixed section 628, or when the second movable section 603 (right) moves toward the first fixed section 628, the structural member 650 will pivot in the relevant direction and begin to flex. Through this pivoting, the structural member 650 can begin to "straighten", that is, the angle between the structural member 650 and the transverse axis can become smaller. Depending on the embodiment, this type of flexure can involve a certain degree of compression and / or stretching and / or bending of the structural member 650. With this configuration, when the actuation force applied to the first movable section 632 or the second movable section 603 is removed, the first movable section 632 or the second movable section 603 will move back to the original position due to the biasing force applied by the structural member 650. Fig. 6A and Figure 6B Relaxed state (first position) shown.
[0124] In an example, an actuator (such as described above and in Figure 1D The actuator 168 shown in FIG. 1 may be configured to selectively and independently actuate movement of the first movable section 632 and the second movable section 603. Alternatively, two such actuators 168 may be provided, in which case the first actuator is coupled to or in contact with the first movable section 632 and the second actuator is coupled to or in contact with the second movable section 603.
[0125] In many other aspects, the configuration of the capillary array device 600 can be the same as described above and in Figure 1A-Figure 1C The capillary array device 100 shown in and / or described above and in Figure 4A and Figure 4B The capillary array device 400 shown in and / or described above and in Figure 5A and Figure 5B The configuration of the capillary array device 500 shown in FIG. 5 is the same or similar. In addition, the capillary array device 600 can be combined with the capillary array device 500 as described above. Figure 1D-1F The components of the sample analysis system described are used in combination.
[0126] As in other embodiments, the capillary array device 600 can be configured for CE, as described herein. In one example, the hole 148 is used as a sample hole, the first slot 152 is used as a (first) gel slot configured to accommodate a (first) CE separation medium, the second slot 156 is used as a buffer slot, and the third slot 611 is used as a (second) gel slot configured to accommodate a (second) CE separation medium (which has a different composition than the first CE separation medium accommodated in the first slot 152).
[0127] A method for analyzing a sample by CE using the capillary array device 600 will now be described. According to the method, the capillary array device 600 is initially set at Fig. 6AIn the first position shown, at the first position, the first capillary end 160 is inside the first groove 152 (first gel groove). The first groove 152 is filled with a desired amount of the first CE separation medium, and the third groove 611 (second gel groove) is filled with a desired amount of the second CE separation medium. The capillary array device 600 is maintained at the first position for a predetermined period of time sufficient to partially fill the 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 in each capillary 124. After the time period assigned for loading the first CE separation medium has passed, the capillary array device 600 is moved to the second position, at which the first capillary end 160 is inside the third groove 611. The capillary array device 600 is maintained 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 a plug of the second CE separation medium in the corresponding capillary 124. According to this method, an axially position-dependent composite CE separation matrix is formed in each capillary 124, wherein each CE separation matrix includes an axial "stacked" arrangement of plugs of different CE separation media. The use of a variety of different CE separation media in the same capillary 124 can provide advantages in the separation and analysis of certain types of samples. Depending on the duration that the capillary array device 600 remains at the first position and the second position, in each capillary 124, the plugs of the first CE separation medium and the plugs of the second CE separation medium may be directly adjacent to each other. Alternatively, the plugs of the first CE separation medium and the plugs of the second CE separation medium may be spatially separated from each other, and the intervening space may be occupied by a buffer solution and / or a sample solution.
[0128] After the time period assigned for loading the second CE separation medium has elapsed, the capillary array device 600 is moved to a third position where the first capillary end 160 is positioned inside the hole 148 (sample hole) and the second capillary end 164 is positioned inside the second groove 156 (buffer groove). Before or after moving to the third position, the hole 148 is filled with a sample and the second groove 156 is filled with a buffer solution. At the third position, the HV source (e.g., Figure 1E The HV source 188 shown) is connected to an electrode (e.g., Figure 1E A circuit is formed between the electrodes 192 shown in Figure 1. A voltage pulse is then applied across the length of the capillary 124 to electrodynamically inject the sample as it is inserted into the front region (first capillary end 160) of the capillary 124. Next, another voltage is applied according to predetermined operating parameters effective for causing electrophoretic separation of different analytes of the sample in each capillary 124, as described elsewhere herein. The measurement can then be performed by an optical-based measurement device (e.g., Figure 1F) detects / measures the separated analytes in each capillary 124 at the detection region 140. Subsequently, as in other embodiments, after acquiring CE data from the sample, the capillary array device 600 can be discarded if desired.
[0129] Fig. 7A and Figure 7B An example of a capillary array device 700 is shown that includes an intrinsic actuator 723. In this example, the intrinsic actuator 723 is a DEA, but may alternatively be configured according to any other example of an intrinsic actuator described herein. Fig. 7A is a longitudinal side elevation view of capillary array device 700 in an unactuated position, which can correspond to a first position as described herein. Figure 7B 7 is a longitudinal side elevation view of capillary array device 700 in an actuated position, which may correspond to a second position, a third position, a fourth position, etc. as described herein. For simplicity, Fig. 7A and Figure 7B Not shown are capillaries 124, as well as certain other features that may be included and described herein, such as receptacles (holes, grooves, etc.).
[0130] In the present example, the movable section 132 is considered to include an intrinsic actuator 723 and a non-intrinsic actuatable component 727, which is coupled to or in contact with (or contactable with) the intrinsic actuator 723. The non-intrinsic actuatable component 727 may be, for example, a component corresponding to the above combination. Figure 1A-1F The material body of the movable section 132 described, which movable section may include one or more of the containers described herein. Also in this example, the capillary array device 700 has an actuator (assembly) 768, which is configured to actuate (or stimulate, activate, etc.) the intrinsic actuator 723. In this example, the actuator 768 includes an actuator 772 in the form of a voltage source, two or more electrodes 731 contacting the upper planar side and the lower planar side of the intrinsic actuator 723, and an electrical (wired) link 776 in the form of a suitable electrical interconnect (e.g., wire) that connects the actuator 772 and the electrodes 731 to form a closed circuit. The electrodes 731 are arranged in parallel and are positioned so that the intrinsic actuator 723 is sandwiched between one or more electrodes 731 located on the upper side and one or more electrodes 731 located on the lower side.
[0131] The capillary array device 700 is actuated by FIG. 7A to FIG. 7B73 is shown by the transition of . In this example, the electrodes 731 are oriented in the transverse (xy) plane. Therefore, the voltage applied by the actuator 772 between the electrodes 731 (and therefore across the thickness of the intrinsic actuator 723) will squeeze the intrinsic actuator 723 in the thickness direction, thereby causing the intrinsic actuator 723 to expand in the transverse plane (in both the x-direction and the y-direction). The intrinsic actuator 723 and the other components of the capillary array device 700 are mounted so that such actuation causes the intrinsic actuator 723 to move the extrinsic actuatable component 727 relative to the capillary, which in this example is in the direction toward the flexible segment 136 (in the Fig. 7A and Figure 7B from the center to the left), such as Figure 7B The movement in turn causes the flexible section 136 to flex according to any of the examples described herein.
[0132] Alternatively, the capillary array device 700 can be configured according to any other embodiment disclosed herein that includes an intrinsic actuator. Thus, the intrinsic actuator 723 can be oriented and / or positioned differently, the intrinsic actuator 723 can be of different types (e.g., SMP, SMA, etc.), the actuating device 772 can be of different types (e.g., heat source, light source, magnetic source, etc.), etc.
[0133] Figure 8 8 is a schematic diagram of an example of a sample analysis system (or device, 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 the capillary array device 100, 300, 40, 500, or 600. The sample analysis system 800 is configured to analyze capillary 124 ( Figure 8 In the context of the present disclosure, the term "optical measurement" encompasses imaging (e.g., microscopic imaging) as well as measurement of more specific characteristics or properties (e.g., presence or absence of an analyte, concentration, mass, charge, quantity, size, etc.), depending on the type of sample analysis system 800. In various examples, the optical measurement can be based on fluorescence, absorbance, luminescence (including chemiluminescence or bioluminescence), (UV, visible or IR) spectroscopy, Raman scattering, microscopy, etc. In general, the structure and operation of the various components provided in an optical-based sample analysis instrument are understood by those skilled in the art and are therefore only briefly described herein to facilitate understanding of the subject matter disclosed herein.
[0134] 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 in the sample analysis system 800 so that the capillaries 124 (or windows thereof) 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 emission light EM emitted from an exposed (optically readable) section of the capillary array device 100. Examples of the photodetector 114 include, but are not limited to, a camera sensitive to the emission wavelength to be detected, a photomultiplier tube (PMT), a photodiode (PD), a charge coupled device (CCD), an active pixel sensor (APS) such as a complementary metal oxide semiconductor (CMOS) device, and the like.
[0135] 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 illuminate the sample in the capillary 124 in the exposure section of the capillary array device 100 by directing the excitation light EX of one or more selected wavelengths. 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 can be provided to enable a user to select a desired excitation wavelength.
[0136] The optical system 106 can further include various types of emission optics 835 configured to transmit emission light EM from the capillary array device 100 to the light detector 114 or additional 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 839 include, but are not limited to (and as needed and as understood by those skilled in the art) lenses, read heads, apertures, optical filters (including, for example, a plurality of selectable filters), light guides, mirrors, beam splitters, beam steering devices, monochromators, diffraction gratings, prisms, optical path switches, and the like.
[0137] The sample analysis system 800 may include an instrument console (or device housing, casing, 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 components associated with the capillary array device 100, such as Figure 1D-1F , Figure 2 as well as Fig. 7A-As shown in FIG. 7F. The instrument console 843 is also configured to prevent stray light from reaching the capillaries 124 and components of the optical system 106 that may be adversely affected by stray light. The instrument console 843 also provides a closed environment for implementing environmental control (e.g., control of temperature, humidity, pressure, etc.) inside the console when necessary. 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 internal areas and components of the sample analysis system 800, etc. As an example, Figure 8 Door 847 is shown which can be opened to allow capillary array device 100 (with or without device support 200) to be loaded into the interior of the console and later removed therefrom, as by Figure 8 851 in the capillary array device 100. The loading / removal of the capillary array device 100 can be done manually or (semi-)automatically. As described herein, the sample and various liquids and / or gels can be pre-loaded in the capillary 124 before the capillary array device 100 is installed in the sample analysis system 800 and the analysis is performed.
[0138] The sample analysis system 800 may also include an actuator 168 (or 768) comprising an actuation device 172 (or 772) and a (contact or non-contact) link 176 (or 776) according to any embodiment described herein. The sample analysis system 800 may also include an HV source 188 configured to apply a voltage (potential difference) across the capillary 124, as described herein.
[0139] The sample analysis system 800 may further include a system controller 855 .
[0140] The system controller 855 generally represents one or more electronically based (e.g., computing) devices or modules, which include various types of hardware (e.g., electronically 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 sample analysis system 800 of the type provided. The system controller 855 can be implemented as one or more types of hardware, such as a circuit board. The system controller 855 can include a data acquisition circuit system (DAC) configured to receive and process the signal output from the photodetector 114 and generate user-interpretable data representing the sample analysis results. The system controller 855 can also be considered to represent a device configured to control, monitor and synchronize the operation of various components of the sample analysis system 800, such as the photodetector 114, the emission optical device 835 (e.g., if a component that consumes power or can be automatically adjusted is included), the light source 110, the excitation optical device 839 (e.g., if a component that consumes power or can be automatically adjusted is included), 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, display monitor, printer, graphical user interface (GUI), etc. The system controller 855 may include an operating system (e.g., Microsoft Windows) for controlling and managing the various functions of the system controller 855. Software). In an example, the system controller 855 is configured to control or execute all or part of any method disclosed herein. For all such purposes, the system controller 855 can communicate with the above-mentioned components via a wired or wireless communication link that enables signal transmission (e.g., transmission of control signals, reception of measurement or feedback signals, etc.).
[0141] An example of a general method for analyzing a sample (particularly requiring the use of a capillary array device 100) will now be described. 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 the capillary 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 in 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. As will be appreciated by those skilled in the art, the sample may undergo various types of preparation or conditioning (incubation, mixing, homogenization, centrifugation, buffering, reagent addition, denaturation, decomposition, cleavage, deprotection, etc.) prior to being placed in the sample analysis system 800, depending on the type of sample analysis being performed.
[0142] After providing the capillary array device 100 as just described, the method includes performing an optical measurement on the sample in the capillary 124 to obtain optical data from one or more analytes of the sample. In a typical example, performing an optical measurement requires irradiating the sample with excitation light EX and collecting the resulting emission light EM emitted from the sample in response to the irradiation. In this example, the optical system 106 of the above-mentioned sample analysis system 800 is operated to perform the optical measurement. In some examples, the excitation light EX causes a photoluminescence (e.g., fluorescence or phosphorescence) response in one or more analytes of the sample, and the optical measurement involves measuring the intensity of the photoluminescent light to quantify one or more analytes (e.g., determine its concentration) or otherwise generate an image of the sample including one or more photoluminescent analytes. In other examples, the excitation light EX is used to irradiate the sample without causing photoluminescence, and the emission light EM is used to measure the absorbance of the sample to quantify one or more analytes or otherwise generate an image of the sample.
[0143] In other examples, the optical measurement does not require irradiation of the sample with excitation light EX. For example, as will be appreciated by those skilled in the art, a reagent that causes luminescence (such as flash luminescence 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 being performed.
[0144] In all such cases, the emission optical device 835 of the optical system 106 of the sample analysis system 800 can be operated to collect the emission light EM from the sample and guide the emission light EM to the light detector 114. The emission light EM can be detected on the same side (e.g., the top side) where the excitation light EX of the capillary array device 100 is incident, or on the opposite side (e.g., excitation is completed on the top side and detection is completed on the bottom side). The light detector 114 then converts the emission light EM into an electrical signal (detection or measurement signal) and transmits the electrical signal to a signal processing circuit system, such as the data acquisition circuit system of the system controller 855 described above.
[0145] In one example, the sample analysis system 800 is configured as a capillary electrophoresis (CE) system. In this case, the capillary 124 contains an electrophoretic separation medium (i.e., an analytical separation medium formulated for CE). In this example, the electrophoretic separation medium is an electrophoretic polymer gel, which can be a polymer formulated for CE as described herein. In order 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 capillary 124, as described herein. The HV source 188 represents various components (such as waveform generators, amplifiers, etc.) required to apply a potential difference having the desired operating parameters (amplitude / amplitude, frequency, one or more waveforms, pulse rate, etc.) for achieving CE, as understood by those skilled in the art.
[0146] Another example of a method for analyzing a sample (particularly in the context of CE) will now be described. The method may generally include the following steps: providing a capillary array device 100; and subsequently optically measuring the sample in the capillary 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 capillary 124 before and / or during the optical measurement (typically performed simultaneously in parallel, but can be performed sequentially). According to a mechanism generally understood by those skilled in the art, the potential difference causes different analytes to migrate through the electrophoretic separation medium at different speeds according to their different sizes and / or charge states. In this way, different analytes become separated from each other, thereby facilitating optical measurement of one or more target analytes of interest in the sample.
[0147] In another example, another type of analytical separation media may be utilized in the capillary 124, such as, for example, a chromatographic separation media.
[0148] Exemplary embodiments Exemplary embodiments provided according to the subject matter disclosed herein include, but are not limited to, the following: 1. A capillary array device, comprising: a capillary array holder, the capillary array holder comprising a fixed section, a movable section, and a flexible section connecting the fixed section and the movable section; and a plurality of capillaries attached to the capillary array holder, wherein the capillaries are arranged in parallel along a device axis of the capillary array holder and are elongated, and wherein: the movable section can move linearly along the device axis relative to the capillaries and the fixed section; and the flexible section flexes in response to movement of the movable section. 2. The capillary array device of embodiment 1, comprising a detection region configured to allow light to be transmitted into and out of the detection region. 3. The capillary array device according to embodiment 2, wherein the fixed section includes the detection area. 4. The capillary array device according to embodiment 2, wherein the movable section includes the detection area. 5. A capillary array device according to any one of the preceding embodiments, wherein the capillary array holder has a total length along the device axis, and the fixed section, the movable section and the flexible section are arranged so that movement of the movable section changes the total length. 6. A capillary array device according to any of the preceding embodiments, wherein the capillary array holder comprises a plurality of holes configured to hold corresponding liquids or gels, and the holes are positioned so that each capillary is aligned with a corresponding one of the holes along the device axis, and wherein the capillaries can move into and out of the corresponding holes in response to movement of the movable section. 7. The capillary array device of embodiment 6, wherein the movable section comprises the hole. 8. The capillary array device of embodiment 6, wherein the fixed section comprises the hole. 9. A capillary array device according to any one of embodiments 6-8, wherein: the capillary includes a corresponding first capillary end and a second capillary end opposite to the first capillary end along the axis of the device; and the movable section is configured to move from a first position to a second position, wherein at the first position, the first capillary end is outside the hole, and at the second position, the first capillary end is inside the hole. 10. The capillary array device of any one of embodiments 6-9, wherein the capillary array holder comprises a plurality of electrodes, and each electrode is positioned in a corresponding one of the holes. 11. A capillary array device according to any of the preceding embodiments, wherein: the capillaries are arranged side by side along a transverse axis orthogonal to the device axis; and the capillary array holder includes a groove extending along the transverse axis and configured to accommodate a liquid or a gel, and the groove is wide enough along the transverse axis to simultaneously receive all of the capillaries. 12. The capillary array device of embodiment 11, wherein the movable section comprises the groove. 13. The capillary array device of embodiment 11, wherein the fixing section comprises the groove. 14. The capillary array device of any one of embodiments 11-13, wherein the capillary array holder comprises an electrode positioned in the groove. 15. A capillary array device according to any one of the preceding embodiments, wherein: the capillaries are arranged side by side along a transverse axis orthogonal to the device axis; the capillaries include a corresponding first capillary end and a second capillary end opposite to the first capillary end along the device axis; the capillary array holder includes a plurality of holes configured to accommodate corresponding liquids or gels, and the holes are positioned so that each first capillary end is aligned with a corresponding one of the holes along the device axis, and wherein the first capillary end can move into and out of the corresponding hole in response to movement of the movable section; and the capillary array holder includes a groove extending along the transverse axis, and the capillary array holder has a configuration according to one of the following: the second capillary end is fixedly disposed in the groove; the first capillary end can move into and out of the groove in response to movement of the movable section. 16. The capillary array device of embodiment 15, wherein the capillary array holder comprises a plurality of electrodes, at least one electrode being positioned in each of the holes, and at least one additional electrode being positioned in the groove. 17. The capillary array device of any one of embodiments 15-16, wherein the movable section comprises the hole, and the fixed section comprises the groove. 18. A capillary array device according to any of the preceding embodiments, wherein: the capillaries are arranged side by side along a transverse axis orthogonal to the device axis; the capillaries include corresponding first capillary ends and second capillary ends opposite to the first capillary ends along the device axis; the capillary array holder includes a plurality of holes configured to accommodate corresponding liquids or gels, and the holes are positioned so that each first capillary end is aligned with a corresponding one of the holes along the device axis, and wherein the first capillary end can move into and out of the corresponding hole in response to movement of the movable section; the capillary array holder includes a first slot, and the first slot is positioned along the transverse axis to align with the first capillary end, and wherein the first capillary end can move into and out of the first slot in response to movement of the movable section; the capillary array holder includes a second slot, the second slot extends along the transverse axis and is configured to receive the second capillary end. 19. The capillary array device of embodiment 18, wherein the movable section comprises the hole and the first groove, and the fixed section comprises the second groove. 20. A capillary array device according to any one of embodiments 18-19, wherein: 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 outside the hole and the first groove; at the second position, the first capillary end is inside the hole; and at the third position, the first capillary end is inside the first groove. 21. A capillary array device according to any one of embodiments 18-20, wherein: the movable section is a first movable section including the hole and the first groove; the capillary array holder further includes a second movable section, which can linearly translate along the device axis relative to the capillary and the fixed section; and the second capillary end can move into and out of the second groove in response to the movement of the second movable section. 22. The capillary array device of embodiment 21, wherein the second movable section comprises the second groove. 23. A capillary array device according to any one of embodiments 21-22, wherein: the capillary array holder further includes a third groove extending along the transverse axis; and the first capillary end can move into and out of the third groove in response to movement of the first movable section. 24. A capillary array device according to embodiment 23, wherein: 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 inside the first groove; at the second position, the first capillary end is inside the third groove; and at the third position, the first capillary end is inside the hole. 25. The capillary array device of embodiment 24, wherein the second movable section is configured to move to the third position, at which the second capillary end is inside the second groove. 26. The capillary array device according to any one of the preceding embodiments, wherein the fixed segment and / or the movable segment comprises a guide feature configured to guide movement of the movable segment. 27. A capillary array device according to embodiment 26, wherein the guide feature includes a leg extending from at least one of the fixed segment or the movable segment, and the leg extends along the device axis adjacent to the other of the fixed segment or the movable segment. 28. A capillary array device according to embodiment 27, wherein the guiding feature includes a recess axially aligned with the leg, and in response to movement of the movable section, the leg moves into the recess or the recess moves around and adjacent to the leg. 29. The capillary array device of any of the preceding embodiments, wherein the flexible section comprises a compliant spring configured to bias the movable member in a direction along the device axis. 30. The capillary array device according to any one of the preceding embodiments, wherein at least a portion of the flexible section is composed of a material that is more flexible than a material of the fixed section and the movable section. 31. The capillary array device of any preceding embodiment, wherein at least a portion of the flexible section has an open frame configuration. 32. The capillary array device of embodiment 31, wherein the open frame configuration comprises a plurality of structural members defining a plurality of holes extending through the flexible segment. 33. The capillary array device of any of the preceding embodiments, wherein at least a portion of the flexible section is interposed between the fixed section and the movable section along the device axis. 34. The capillary array device of any of the preceding embodiments, wherein at least a portion of the flexible segment is between the fixed segment and the movable segment along a transverse axis orthogonal to the device axis. 35. The capillary array device of any preceding embodiment, wherein the movable segment comprises a feature configured to be coupled to or contacted by an actuator. 36. The capillary array device of any preceding embodiment, comprising an actuator configured to move the movable section. 37. The capillary array device of embodiment 36, wherein the actuator comprises an actuating device and a mechanical link, wherein the mechanical link is coupled to the actuating device and coupled to the movable segment or is capable of contacting the movable segment. 38. The capillary array device of embodiment 36, wherein the actuator comprises an intrinsic actuator and an actuating device, wherein the actuating device is configured to cause actuation of the intrinsic actuator. 39. A capillary array device according to embodiment 38, wherein the intrinsic actuator is selected from: a dielectric elastomer actuator; a shape memory polymer; a shape memory alloy; and a magnet. 40. The capillary array device of any one of embodiments 38-39, wherein the actuation device is selected from: a voltage source; a heat source; a light source; and a magnetic source. 41. The capillary array device of any one of embodiments 38-40, wherein the movable segment and / or the flexible segment comprises the intrinsic actuator. 42. A sample analysis system, comprising: a capillary array device according to any one of the preceding embodiments; and a light detector positioned in optical alignment with the capillary to receive light emitted from the capillary. 43. A sample analysis system according to embodiment 42, comprising a light source, which is positioned to be optically aligned with the detection area to transmit light to the capillary. 44. The sample analysis system of any one of embodiments 42-43, comprising a voltage source configured to apply a potential difference across the capillary. 45. A sample analysis system according to embodiment 44, wherein the voltage source is configured to apply a potential difference according to operating parameters effective for capillary electrophoresis of a sample disposed in the capillary. 46. The sample analysis system of any one of embodiments 42-45, comprising an actuator configured to actuate movement of the movable section. 47. A sample analysis system according to embodiment 46, wherein the actuator includes features selected from: a mechanical or electromechanical actuation device connected to a movable mechanical link; a voltage source; a heat source; a light source; and a magnetic source. 48. The sample analysis system of any one of embodiments 42-47, comprising a device support configured to support the capillary array device in a fixed position. 49. A method for injecting a liquid or gel into a plurality of capillaries, the method comprising: providing a capillary array device, the capillary array device comprising the plurality of capillaries and a capillary array holder, wherein the capillary array holder comprises a fixed section, a movable section and a flexible section connecting the fixed section and the movable section, and the capillaries are attached to the capillary array holder and are arranged in parallel along a device axis of the capillary array holder and are elongated; moving the movable section along the device axis to a position at which the capillaries extend into one or more containers of the capillary array holder, wherein the liquid or gel is contained in the one or more containers and the flexible section flexes in response to the movement of the movable section; and injecting the liquid or gel from the one or more containers into the capillaries by capillary action. 50. A method according to embodiment 49, wherein the injecting includes applying a voltage across each of the capillaries along the axis of the device to electrodynamically assist the injection. 51. A method according to any one of embodiments 49-50, comprising, after the injection, applying a voltage across each of the capillaries along the device axis to electrodynamically cause the liquid or gel in each capillary to flow through the capillary. 52. A method according to any one of embodiments 49-51, wherein the container respectively contains a sample to be analyzed, and the injecting includes injecting the sample into the capillary accordingly. 53. A method according to embodiment 52, comprising applying a voltage across each of the capillaries along the axis of the device after the injecting, wherein the voltage is applied according to operating parameters effective for capillary electrophoresis of the sample. 54. A method according to any one of embodiments 49-53, wherein the one or more containers include a plurality of holes and each capillary is aligned with a corresponding one of the holes along the device axis. 55. The method of any one of embodiments 49-54, wherein the one or more containers comprise a groove, and after the moving, the capillaries each extend into the groove. 56. A method according to any one of embodiments 49-55, wherein: the capillary comprises a corresponding first capillary end and a second capillary end; the one or more containers comprise a plurality of holes, and the first capillary end can move into and out of the corresponding holes in response to movement of the movable section, and the liquid or gel injected from the holes is the first liquid or first gel injected through the first capillary end; the capillary array holder comprises a groove, which accommodates a second liquid or a second gel; and the method further comprises one of the following: injecting the second liquid or the second gel into the second capillary end by capillary action; moving the movable section along the axis of the device to a position at which the first capillary end extends into the groove and the second liquid or the second gel is injected into the first capillary end by capillary action. 57. A method according to any one of embodiments 49-56, wherein: the capillary comprises a corresponding first capillary end and a second capillary end; the one or more containers comprise a plurality of holes, and the first capillary end can move into and out of the corresponding holes in response to movement of the movable section, and the liquid or gel injected from the holes is the first liquid or the first gel injected through the first capillary end; the capillary array holder comprises a first groove, the first groove accommodating a second liquid or a second gel; the capillary array holder comprises a second groove, the second groove accommodating a third liquid or a third gel; and the method further comprises: injecting the second liquid or the second gel into the first capillary end by capillary action; and injecting the third liquid or the third gel into the second capillary end by capillary action. 58. A method according to embodiment 57, wherein: the movable section is a first movable section, and the capillary array holder includes a second movable section; and before injecting the third liquid or third gel into the second capillary end, the second movable section is moved along the device axis to a position at which the second capillary end extends into the second groove. 59. A method according to embodiment 58, wherein: the capillary array holder includes a third groove, the third groove accommodating a fourth liquid or a fourth gel; and the method further includes injecting the fourth liquid or the fourth gel into the first capillary end by capillary action after injecting the second liquid or the second gel into the first capillary end. 60. A method according to any one of embodiments 49-59, wherein the movement of the movable section is performed manually. 61. A method according to any one of embodiments 49-59, wherein the movement of the movable section includes actuating the movement of the movable section. 62. A method according to embodiment 61, wherein the actuation includes moving an actuator into contact with the movable section, or operating an actuator connected to the movable section. 63. A method according to embodiment 61, wherein the actuation includes magnetically coupling the actuator to a magnet of the capillary array holder. 64. The method of embodiment 61, wherein the actuation comprises activating an intrinsic actuator of the capillary array holder. 65. A method according to embodiment 64, wherein the activation is selected from: applying an electric field to the intrinsic actuator, wherein the intrinsic actuator comprises a dielectric elastomer actuator; applying thermal energy to the intrinsic actuator, wherein the intrinsic actuator comprises a shape memory polymer; applying a light beam to the intrinsic actuator, wherein the intrinsic actuator comprises a shape memory polymer; applying an electric field to the intrinsic actuator, wherein the intrinsic actuator comprises a shape memory polymer; applying a magnetic field to the intrinsic actuator, wherein the intrinsic actuator comprises a shape memory polymer; and applying thermal energy to the intrinsic actuator, wherein the intrinsic actuator comprises a shape memory alloy. 66. A method for analyzing a sample, comprising: injecting the liquid or gel into the capillary according to the method described in any one of embodiments 49-65, wherein the liquid or gel includes a sample to be analyzed, and the injection includes injecting the sample into the capillary accordingly; and optically measuring the sample in the capillary to obtain optical data from one or more analytes of the sample. 67. A method according to embodiment 66, wherein performing the optical measurement includes detecting emission light emitted from the capillary. 68. A method according to any one of embodiments 66-67, wherein performing the optical measurement includes illuminating the sample with excitation light. 69. A method according to any one of embodiments 66-68, comprising analytically separating the sample in each capillary before and / or during performing the optical measurement. 70. A method according to embodiment 69, wherein analytically separating the sample includes performing capillary electrophoresis on the sample.
[0149] It will be understood that terms such as "communication" and "in communication" (e.g., a first component is "in communication" or "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. Thus, the fact that one component is said to be in communication with a second component is not intended to exclude the possibility that additional components may exist between the first component and the second component and / or be operably associated or engaged with the first component and the second component.
[0150] It will 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 the purpose of illustration only, and not for the purpose of limitation, the invention being defined by the claims.
Claims
1. A capillary array device, comprising: A capillary array holder, the capillary array holder comprising a fixed section, a movable section, and a flexible section connecting the fixed section and the movable section; as well as a plurality of capillaries attached to the capillary array holder, wherein the capillaries are arranged in parallel and elongated along a device axis of the capillary array holder, and wherein: The movable section is linearly movable along the device axis relative to the capillary and the fixed section; and The flexible section flexes in response to movement of the movable section.
2. The capillary array device according to claim 1, wherein: The capillary array holder comprises a plurality of wells configured to hold respective liquids or gels, and the wells are positioned such that each capillary is aligned with a respective one of the wells along the device axis, and wherein the capillaries are movable into and out of the respective wells in response to movement of the movable segment.
3. The capillary array device according to claim 2, wherein: The capillary comprises a respective first capillary end and a second capillary end opposite the first capillary end along the device axis; and The movable section is configured to move from a first position, where the first capillary end is outside the aperture, to a second position, where the first capillary end is inside the aperture.
4. The capillary array device according to claim 2, wherein: The capillary array holder includes a plurality of electrodes, and each electrode is positioned in a corresponding one of the holes.
5. The capillary array device according to claim 1, wherein: The capillaries are arranged side by side along a transverse axis orthogonal to the device axis; and The capillary array holder includes a slot extending along the transverse axis and configured to contain a liquid or a gel, and the slot is sufficiently wide along the transverse axis to simultaneously receive all of the capillaries.
6. The capillary array device according to claim 5, wherein: The capillary array holder includes an electrode positioned in the groove.
7. The capillary array device of claim 1, wherein: The capillaries are arranged side by side along a transverse axis orthogonal to the axis of the device; The capillary tube includes a respective 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 configured to receive respective liquids or gels, and the wells are positioned such that each first capillary end is aligned with a respective one of the wells along the device axis, and wherein the first capillary ends are movable into and out of the respective wells in response to movement of the movable section; and The capillary array holder includes a slot extending along the transverse axis, and the capillary array holder has a configuration according to one of the following: the second capillary end is disposed in the slot in a fixed manner; the first capillary end can be moved into and out of the slot in response to movement of the movable section.
8. The capillary array device of claim 1, wherein: The capillaries are arranged side by side along a transverse axis orthogonal to the axis of the device; The capillary tube includes a respective 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 configured to receive respective liquids or gels, and the wells are positioned such that each first capillary end is aligned with a respective one of the wells along the device axis, and wherein the first capillary ends are movable into and out of the respective wells in response to movement of the movable segment; The capillary array holder includes a first slot, and the first slot is positioned along the transverse axis to align with the first capillary end, and wherein the first capillary end is movable into and out of the first slot in response to movement of the movable section; The capillary array holder includes a second groove extending along the transverse axis and configured to receive the second capillary end.
9. The capillary array device of claim 8, wherein: 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 outside the hole and the first groove; At the second position, the first capillary end is inside the hole; and In the third position, the first capillary end is inside the first groove.
10. The capillary array device according to claim 8, wherein: The movable section is a first movable section including the hole and the first slot; The capillary array holder further comprises a second movable section that is linearly translatable relative to the capillaries and the fixed section along the device axis; and The second capillary end is movable into and out of the second groove in response to movement of the second movable section.
11. The capillary array device of claim 10, wherein: The capillary array holder further comprises a third groove extending along the transverse axis; and The first capillary end is movable into and out of the third slot in response to movement of the first movable section.
12. The capillary array device of claim 11, wherein: 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 inside the first groove; At the second position, the first capillary end is inside the third groove; and In the third position, the first capillary end is inside the hole.
13. The capillary array device according to claim 12, wherein: The second movable section is configured to move to the third position where the second capillary end is inside the second groove.
14. The capillary array device according to claim 1, wherein: The flexible section includes at least one of the following features: The flexible section includes a compliant spring configured to bias the movable member in a direction along the device axis; at least a portion of the flexible section is constructed of a material that is more flexible than the material of the fixed section and the movable section; at least a portion of the flexible section has an open frame configuration; At least a portion of the flexible section has an open frame configuration, and the open frame configuration includes a plurality of structural members defining a plurality of holes extending through the flexible section; At least a portion of the flexible section is interposed along the device axis between the fixed section and the movable section; At least a portion of the flexible section is interposed between the fixed section and the movable section along a transverse axis orthogonal to the device axis.
15. The capillary array device of claim 1, comprising an actuator configured to move the movable section.
16. The capillary array device according to claim 15, wherein: The actuator includes at least one of the following features: an actuating device and a mechanical link coupled to the actuating device and coupled to or contactable with the movable section; an intrinsic actuator and an actuation device, the actuation device being configured to cause actuation of the intrinsic actuator; An intrinsic actuator and an actuation device, the actuation device being configured to cause actuation of the intrinsic actuator, wherein the intrinsic actuator is selected from: a dielectric elastomeric actuator; a shape memory polymer; a shape memory alloy; and a magnet; An intrinsic actuator and an actuation device configured to cause actuation of the intrinsic actuator, wherein the actuation device is selected from: a voltage source; a heat source; a light source; and a magnetic source; An intrinsic actuator and an actuation device, the actuation device being configured to cause actuation of the intrinsic actuator, wherein the movable section and / or the flexible section comprises the intrinsic actuator.
17. The capillary array device of claim 1, comprising a plurality of electrodes configured to apply a potential difference according to operating parameters effective for performing capillary electrophoresis on a sample disposed in the capillary.
18. A sample analysis system, comprising: The capillary array device according to claim 1; as well as A light detector is positioned in optical alignment with the capillary to receive light emitted from the capillary.
19. A method for injecting a liquid or a gel into a plurality of capillaries, the method comprising: A capillary array device is provided, the capillary array device comprising the plurality of capillaries and a capillary array holder, wherein: The capillary array holder includes a fixed section, a movable section, and a flexible section connecting the fixed section and the movable section; and The capillaries are attached to the capillary array holder and are arranged in parallel along a device axis of the capillary array holder and are elongated; moving the movable section along the device axis to a position at which the capillaries extend into one or more containers of the capillary array holder, wherein the liquid or gel is contained in the one or more containers, and the flexible section flexes in response to the movement of the movable section; and The liquid or gel is injected from the one or more containers into the capillary tube by capillary action.
20. A method for analyzing a sample, comprising: Injecting the liquid or gel into the capillary according to the method of claim 19, wherein the liquid or gel comprises a sample to be analyzed and the injecting comprises injecting the sample into the capillary accordingly; and An optical measurement is performed on the sample in the capillary to obtain optical data from one or more analytes in the sample.