Systems and methods for capillary electrophoresis, isoelectric point and molecular weight analysis

Abstract

The present invention relates to a system comprising a housing, a box holder arranged in the housing, a detection assembly arranged in the housing and a reagent tray holder movably arranged in the housing. The box holder is configured to receive a capillary box with a capillary. The detection assembly comprises at least one emitter, a first detector and a second detector. The detection assembly is configured to switch between a first configuration and a second configuration, wherein the first detector detects a first output of at least one emitter in the first configuration, and the second detector detects a second output of at least one emitter in the second configuration. The reagent tray holder is configured to move relative to the box holder, so that the capillary of the capillary box is placed in communication with a reagent volume fluid.

Description

[0001] This application is a divisional application of the invention patent application entitled “System and method for capillary electrophoresis, isoelectric point and molecular weight analysis”, filed on January 13, 2017, with international application number PCT / US2017 / 013470 and national application number 201780015587.5.

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS

[0003] This application claims the benefit of U.S. Provisional Patent Application No. 62 / 278,159, filed on January 13, 2016, the entire disclosure of which is incorporated herein by reference. Technical Field

[0004] Embodiments described herein generally relate to systems and methods for electrophoretically separating and / or analyzing sample mixtures by molecular weight and / or isoelectric point. Certain embodiments described herein relate to separation, detection, identification, classification and / or quantification of an analyte or multiple analytes present in a sample. More specifically, embodiments described herein relate to systems and methods configured to perform capillary-based electrophoresis. Background Art

[0005] Electrophoresis has been used to separate mixtures of molecules based on their different rates of travel in an electric field. In general, electrophoresis refers to the movement of suspended or dissolved molecules through a fluid or gel under the action of an electromotive force applied to one or more electrodes or conductive members in contact with the fluid or gel. Certain known modes of electrophoretic separation include separating molecules based at least in part on differences in the mobility of molecules in a buffer solution (commonly known as zone electrophoresis), in a gel or polymer solution (commonly known as gel electrophoresis), or in a pH gradient (commonly known as isoelectric focusing). The movement of molecules during electrophoresis can be highly variable, explained by comparison with electrophoresis standards, the behavior and personality of which have been previously characterized. Electrophoresis standards include, for example, molecular weight (MW) standards in polyacrylamide gel electrophoresis (SDS-PAGE) and deoxyribonucleic acid (DNA) size standards in agarose gels. In some cases, biomolecule separations can be performed in capillaries by capillary electrophoresis. In some cases, biomolecules (eg, proteins) can then be visualized by immobilizing the biomolecules to the capillary walls. However, capillary electrophoresis and biomolecule visualization can be difficult to perform consistently.

[0006] Biomolecule visualization can be performed using digital imaging. This known analysis uses an imaging device (e.g., a charge coupled device, a photodiode, and / or the like) and a lens or microscope to capture an image of a sample and / or otherwise detect the sample. In some cases, the light source flashes at a higher rate as the sample flows through an optical device to illuminate the flowing biomolecules in a column (e.g., a capillary) and / or otherwise allow imaging of the flowing biomolecules in a column (e.g., a capillary). The captured image is filtered and / or isolated, for example, to produce an image of a feature associated with the biomolecule, such as label fluorescence, native fluorescence, and / or absorbance. This information can then be compared with known data to characterize and / or identify the biomolecules in the sample.

[0007] Although some methods are used to perform electrophoretic analysis to determine information associated with an analyte, protein, molecule, or the like, these methods are typically performed in complex and expensive devices capable of performing a single analysis mode. In addition, some known methods and systems involve extensive and / or time-consuming handling and processing steps that adversely affect reproducibility and make automation difficult.

[0008] Thus, there is a need for improved systems and methods that are configured to perform multiple types of analyses, such as electrophoretic mobility and / or isoelectric focusing, within a single device. It is also desirable to automate such techniques so that multiple samples can be analyzed simultaneously or in rapid succession with ease of use and robustness while consuming a minimum amount of expensive reagents and / or disposables. Summary of the invention

[0009] This paper describes systems and methods for capillary electrophoresis and analyte visualization and characterization. In one aspect, a system includes a housing, a box holder arranged in the housing, a detection assembly arranged in the housing, and a reagent tray holder movably arranged in the housing. The box holder is configured to receive a capillary box with a capillary. The detection assembly includes at least one emitter, a first detector and a second detector. The detection assembly is configured to switch between a first configuration and a second configuration, wherein the first detector detects a first output of at least one emitter in the first configuration, and the second detector detects a second output of at least one emitter in the second configuration. The reagent tray holder is configured to move relative to the box holder, so that the capillary of the capillary box is placed in communication with a reagent volume fluid.

[0010] In another aspect, an apparatus includes a cartridge body, a capillary disposed within the cartridge body, a conductive vial disposed within the cartridge body, a first electrode electrically coupled to the conductive vial, and a second electrode. The capillary defines an internal volume configured to accommodate a sample containing an analyte. The capillary has a first end and a second end, the first end defining a first end of the internal volume, and the second end defining a second end of the internal volume. The conductive vial includes a buffer and has a first diaphragm and a second diaphragm. The buffer is electrically coupled to the first end of the internal volume of the capillary via the first diaphragm so that the sample is electrically coupled to the vial when the internal volume accommodates the sample. The second electrode is electrically coupled to the second end of the capillary so that the first electrode, the second electrode, and the sample define portions of a circuit when the internal volume accommodates the sample. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] Figure 1 is a schematic diagram of a portion of a system configured to perform capillary electrophoresis and / or image analytes separated by capillary electrophoresis according to an embodiment.

[0012] Figure 2 is a perspective view of a system configured to perform capillary electrophoresis and / or image analytes separated by capillary electrophoresis, according to an embodiment.

[0013] Figure 3 and Figure 4 They are included in Figure 2 Perspective and exploded views of the door assembly in the housing of the system shown in .

[0014] Figure 5 and Figure 6 yes Figure 2 A front perspective view of a portion of the system shown in FIG. 1 , showing portions without the housing, and showing Figure 3 The door assembly is in an open configuration and a closed configuration, respectively.

[0015] Figures 7 to 9 are various perspectives, each showing Figure 2 The different parts of the system are shown in .

[0016] Fig.10 and Fig.11 They are Figure 3 Front and rear perspective views of portions of the reagent assembly and housing of the system shown in .

[0017] Fig.12 yes Fig.10 An exploded view of the tray portion of the reagent assembly is shown in FIG.

[0018] Fig.13 It is shown Figure 2 A rear perspective view of a portion of the system shown in FIG.

[0019] Fig.14 is included in Figure 2 Front perspective view of the capillary cartridge holder and optical components of the system.

[0020] Fig.15 yes Fig.14 A front perspective view of the capillary cartridge holder shown in FIG.

[0021] Fig.16 yes Fig.14 A partial exploded view of the capillary cartridge holder shown in FIG.

[0022] Figures 17 to 19 They are Fig.14 , a right rear perspective view, a left front perspective view, and a front view of a portion of a capillary cartridge holder shown in FIG.

[0023] Fig. 20 yes Fig.14 Capillary cartridge holder and Fig.14 A perspective view of the single-point detection portion of the optical assembly.

[0024] Fig.21 yes Fig. 20 A perspective view of the single point detection portion of the optical assembly is shown in FIG.

[0025] Fig. 22 yes Fig. 20 An exploded view of the single point detection portion of the optical assembly is shown in FIG.

[0026] Fig.23 It is along Fig.21 A cross-sectional view of the single-point detection portion of the optical assembly taken along line 23-23 in FIG.

[0027] Fig.24 yes Fig.14 The box holder and Fig.14 A perspective view of the full column detection portion of the optical assembly is shown in FIG.

[0028] Fig.25 and Fig.26 They are included in Fig.24 A perspective view and exploded view of the illumination assembly in the full column detection portion of the optical assembly shown in FIG.

[0029] Fig. 27 and Fig.28 They are included in Fig.24 Perspective and exploded views of the camera assembly in the full column detection portion of the optical assembly shown in .

[0030] Fig.29 and Fig.30 are configured to be used during molecular weight analysis Figure 2 Left and right perspective views of a capillary cartridge used in a system of FIG.

[0031] Fig.31 The part without the box body is shown Fig.29 Side view of the capillary cartridge.

[0032] Fig.32 and Fig.33 Respectively, maintain Fig.14 The capillary cartridge holder shown in Fig.29 0046] Figure 2 is a right perspective view and a left perspective view of the capillary cartridge shown in FIG.

[0033] Fig.34 is shown without side walls Fig.14 Capillary cartridge holder and Fig.29 Left side perspective view of the capillary box.

[0034] Fig.35 It is along Fig.31 35 - 35 in FIG. 2 , a cross-sectional view of a capillary cartridge and a capillary cartridge holder taken along line 35 - 35 in FIG.

[0035] Fig.36 yes Fig.29 Capillary box, Fig. 20 The single point detection portion of the optical assembly shown in Fig.14 Front perspective view of a portion of the capillary cartridge holder.

[0036] Fig.37 It is along Fig.36 A cross-sectional view of the capillary cartridge, the single point detection portion of the optical assembly, and the capillary cartridge holder taken along line 37-37 in FIG.

[0037] Fig.38 and Fig.39 are configured to be used during capillary electrophoresis analysis Figure 2 Left and right perspective views of a capillary cartridge used in a system of FIG.

[0038] Fig.40 and Fig.41 The part without the box body is shown Fig.38 Side and perspective views of the capillary box.

[0039] Fig.42 yes Fig.38 Capillary box, Fig.24 The full column imaging section of the optical assembly shown in Fig.14 A perspective view of a cartridge holder.

[0040] Fig.43 is to keep Fig.14 The capillary cartridge holder shown in Fig.38 Left side perspective view of the capillary box.

[0041] Fig.44 It is along Fig.43 44-44 of the capillary cartridge and the capillary cartridge holder. DETAILED DESCRIPTION

[0042] Devices, methods and systems for performing capillary electrophoresis, isoelectric point and / or molecular weight analysis of a sample are described herein. The devices and systems are configured to detect analytes within a sample during and / or after electrophoretic separation.

[0043] In certain embodiments, a system comprises a housing, a box holder arranged in the housing, a detection assembly arranged in the housing, and a reagent tray holder movably arranged in the housing. The box holder is configured to receive a capillary box with a capillary. The detection assembly comprises at least one emitter, a first detector and a second detector. The detection assembly is configured to switch between a first configuration and a second configuration, wherein the first detector detects a first output of at least one emitter in the first configuration, and the second detector detects a second output of at least one emitter in the second configuration. The reagent tray holder is configured to move relative to the box holder, so that the capillary of the capillary box is placed in communication with the reagent volume fluid.

[0044] In certain embodiments, a system includes a housing, a cartridge holder disposed in the housing, a light source disposed in the housing, and a detection assembly disposed in the housing. The cartridge holder includes a first side portion and a second side portion. The first side portion and the second side portion are substantially parallel and define a space configured to receive at least part of a capillary cartridge therebetween. Each of the first side portion and the second side portion defines a first opening and a second opening. The first opening and the second opening of the second side portion are substantially aligned with the first opening and the second opening of the first side portion, respectively. The light source is configured to emit a first light beam and a second light beam. At least part of the first light beam is directed through the first opening of the first side portion and the first opening of the second side portion. At least part of the second light beam is directed through the second opening of the first side portion and the second opening of the second side portion. The detection assembly includes a first detector and a second detector, wherein the first detector is configured to detect at least part of the first light beam, and the second detector is configured to detect at least part of the second light beam.

[0045] In certain embodiments, a system comprises a housing, a box holder arranged in the housing, a detection assembly arranged in the housing, a reagent tray holder movably arranged in the housing, and a control assembly arranged in the housing. The box holder is configured to receive a capillary box with a capillary. The box holder comprises a plurality of contact surfaces, and the plurality of contact surfaces are configured to contact the capillary box and align the capillary box in the box holder. The detection assembly comprises a first emitter and a second emitter and a first detector and a second detector. The detection assembly is configured to switch between a first configuration and a second configuration based at least in part on one or more features associated with the capillary box. The first detector is configured to detect the output of the first emitter when the detection assembly is in the first configuration. The second detector is configured to detect the output of the second emitter when the detection assembly is in the second configuration. The reagent tray holder is configured to move relative to the box holder, so that the capillary of the capillary box is placed in communication with the reagent volume fluid. The control assembly is configured to receive data associated with the capillary box when the capillary box is arranged in the box holder. The control assembly is configured to send a signal to the detection assembly to place the detection assembly in the first configuration or the second configuration based on data associated with the capillary cartridge.

[0046] In certain embodiments, a device includes a cartridge body, a capillary disposed within the cartridge body, a conductive vial disposed within the cartridge body, a first electrode electrically coupled to the conductive vial, and a second electrode. The capillary defines an internal volume configured to accommodate a sample containing an analyte. The capillary has a first end and a second end, the first end defining a first end of the internal volume, and the second end defining a second end of the internal volume. The conductive vial includes a buffer and has a first diaphragm and a second diaphragm. The buffer is electrically coupled to the first end of the internal volume of the capillary via the first diaphragm so that the sample is electrically coupled to the vial when the internal volume accommodates the sample. The second electrode is electrically coupled to the second end of the capillary so that the first electrode, the second electrode, and the sample define portions of a circuit when the internal volume accommodates the sample.

[0047] In certain embodiments, an apparatus includes: a cartridge body configured to be disposed within an analyzer; a capillary disposed within the cartridge body; and a tube disposed within the cartridge body. The cartridge body defines an opening. The capillary is configured for analyte separation. The tube is coupled to an end of the capillary so that the analyzer can apply at least one of pressure or vacuum to the capillary. At least a portion of the tube is exposed via the opening. The opening is configured to receive a portion of a pinch valve from the analyzer. The pinch valve is configured to clamp the tube.

[0048] In certain embodiments, an apparatus includes: a cartridge body configured to be disposed within an analyzer; a capillary disposed within the cartridge body; an outlet tube; an outlet port fluidly coupled to the outlet tube; and a waste container defined within the cartridge body. The capillary is configured for analyte separation. A capillary having an outlet is disposed within the cartridge body. The outlet tube is coupled to the capillary output. The waste container is fluidly coupled to the outlet tube and configured to prevent liquid from flowing from the outlet tube to the outlet port.

[0049] In certain embodiments, an apparatus includes: a cartridge body configured to be disposed within an analyzer; a capillary disposed within the cartridge body; a buffer disposed in a vial within the cartridge body; a first diaphragm disposed between the buffer and the capillary; and a second diaphragm disposed between the buffer and the analyzer. The capillary is configured to separate analytes based on isoelectric point. The buffer is configured to induce a pH gradient along the length of the capillary. The second diaphragm is configured to be broken by the analyzer so that at least one of pressure or vacuum can be applied to the vial.

[0050] As used in this specification, the singular forms "a", "an", and "the" include plural referents unless the context clearly indicates otherwise. Thus, for example, the term "component" is intended to mean a single component or a combination of components, and "material" is intended to mean one or more materials or a combination thereof.

[0051] As used herein, the terms "about" and "approximately" generally mean the stated value plus or minus 10%. For example, about 0.5 would include 0.45 and 0.55, about 10 would include 9 to 11, and about 1000 would include 900 to 1100.

[0052] As used herein, the term "a set" may refer to a plurality of features or a single feature having multiple parts. For example, when referring to a set of walls, a set of walls may be considered to be a wall having multiple parts, or a set of walls may be considered to be a plurality of different walls. Thus, an integrally constructed item may include a set of walls. The set of walls may include multiple parts that are continuous or discontinuous with respect to one another. A set of walls may also be made from multiple items that are produced separately and subsequently joined together (e.g., via welding, adhesives, or any suitable method).

[0053] As used herein, the terms "perpendicular" and / or "orthogonal" generally describe a relationship between two geometric configurations (e.g., two lines, two planes, a line and a plane, or similar geometric configurations) where the two geometric configurations are arranged at substantially 90°. For example, when the lines intersect at an angle substantially equal to 90°, the line is said to be "perpendicular" to another line. Similarly, when a plane (e.g., a two-dimensional surface) is said to be "orthogonal" to another plane, as the planes extend to infinity, the planes are arranged at substantially 90° (e.g., substantially perpendicular).

[0054] As used herein, the term "module" refers to any assembly and / or group of operably coupled electronic components, which may include, for example, memory, processors, electrical traces, optical connectors, software (implemented in hardware), and / or the like. For example, a module executed in a processor may be any combination of hardware-based modules (e.g., field programmable gate arrays (FPGAs), application-specific integrated circuits (ASICs), digital signal processors (DSPs)) and / or software-based modules (e.g., modules of computer code stored in memory and / or executed at a processor) that are capable of performing one or more specific functions associated with the module.

[0055] As used herein, the term "analyte" and / or "target analyte" refers to any molecule or compound to be separated and / or detected by the methods, devices and systems provided herein. Suitable analytes include, but are not limited to, small chemical molecules, e.g., environmental molecules, clinical molecules, chemicals, pollutants and / or biomolecules. More specifically, such chemical molecules may include, but are not limited to, pesticides, insecticides, toxins, therapeutic agents and / or drugs of abuse, antibiotics, organic substances, hormones, antibodies, antibody fragments, antibody molecule conjugates (e.g., antibody drug conjugates), antigens, cell membrane antigens, proteins (e.g., enzymes, immunoglobulins and / or glycoproteins), nucleic acids (e.g., DNA and / or RNA), lipids, lectins, carbohydrates, whole cells (e.g., prokaryotic cells such as pathogenic bacteria and / or eukaryotic cells such as mammalian tumor cells), viruses, spores, polysaccharides, glycoproteins, metabolites, coenzyme factors, nucleotides, polynucleotides (including RNA and / or DNA), transition state analogs, inhibitors, receptors, receptor ligands (e.g., neuroreceptors or their ligands, hormone receptors or their ligands, nutrient receptors or their ligands, and / or cell surface receptors or their ligands), receptor-ligand complexes, nutrients, electrolytes, growth factors and other biological molecules and / or non-biological molecules, as well as fragments and combinations thereof. In certain embodiments, the analyte is a protein or protein complex and the sample is a cell lysate or purified protein.Other suitable analytes may include aggregates, agglomerates, floccules, and / or droplets or particles of the dispersed phase of a colloid and / or emulsion.

[0056] As used herein, the term "sample" refers to a composite containing one or more analytes to be detected. In certain embodiments, the sample is heterogeneous, containing various components (e.g., different proteins), or the sample is homogeneous, containing a component (e.g., a group of proteins). In some cases, the sample can be a naturally generated biological material and / or an artificial material. In addition, the sample can be a natural form (e.g., a cell suspension) or a denatured form (e.g., a lysate). In some cases, the sample can be a single cell (or the content of a single cell, for example, such as a cell lysate from a single cell, or a purified protein) or a plurality of cells (or the content of a plurality of cells, for example, such as a cell lysate from a plurality of cells or a purified protein from a plurality of cells), a blood sample, a tissue sample, a skin sample, a urine sample, a water sample, and / or a soil sample. In some cases, the sample can come from an organism, for example, a eukaryote, a prokaryote, a mammal, a human, a yeast and / or a bacterium, or the sample can come from a virus.

[0057] In certain embodiments, the sample is a heterogeneous biological sample or a mixture of biological molecules such as a heterogeneous biological sample, for example, a tissue lysate, a cell lysate or a mixture of biological molecules such as a protein (for example, a purified protein). In another embodiment, the protein in the cell lysate is an analyte to be detected by the method and system described herein. In yet another embodiment, the device, system and method provided herein are provided for detecting a specific form of protein, for example, a phosphorylated protein. For example, a cell lysate can be a lysate of a cell or a lysate of a mixture of cells. In addition, the cell lysate can include a single cell type or multiple cell types. In certain embodiments, the cell type includes a stem cell or a cancer cell or a group of stem cells or a group of cancer cells. In certain embodiments, the sample includes one or more stem cells (for example, any cell that can divide in an uncertain time period to produce a specialized cell). Suitable examples of stem cells can include, but are not limited to, embryonic stem cells (for example, human embryonic stem cells (hES)) and non-embryonic stem cells (for example, mesenchymal stem cells, hematopoietic stem cells, induced pluripotent stem cells (iPS cells) or adult stem cells (MSC)).

[0058] In some cases, before the analyte in the sample is detected by the equipment and system provided herein, the sample can be processed. For example, the sample can be subjected to a lysis step, a denaturation step, a heating step, a purification step (e.g., protein purification), a precipitation step, an immunoprecipitation step, a column chromatography step, centrifugation, etc. In certain embodiments, the sample is subjected to a denaturation step before the target analyte in the sample is detected and / or separated by the method, equipment and system provided herein. In certain embodiments, the processing step of the sample is performed in one of the equipment or systems described herein. In another embodiment, the processing step is performed before the sample is introduced into one of the equipment or systems set forth herein.

[0059] As used herein, the terms "standard" and / or "internal standard" refer to a well-characterized substance of known quantity and / or identity (e.g., known isoelectric point, molecular weight, electrophoretic mobility distribution, number of base pairs in the case of nucleic acids, molecular structure, etc.) that can be added to a sample including an analyte for comparison purposes. In certain embodiments, a known amount of a standard is added to a sample including one or more analytes, and both the standard and the molecules in the sample including one or more analytes are separated by electrophoresis based on isoelectric point. Comparison of the standard and analyte signals then provides a quantitative or semi-quantitative measurement of the amount of analyte originally present in the sample.

[0060] In some embodiments, the standard of isoelectric focusing (IEF) is known based on the isoelectric point of the establishment. Similarly, molecular weight standards are known. In some cases, the standard and / or one or more analytes can be detected by means of one or more detection molecules or reagents, for example, by means of antibodies for analytes or the label part (moiety) attached to the standard to detect. In certain embodiments, the primary antibody is used to bind the target analyte, and the secondary antibody coupled to the fluorescent or chemiluminescent reagent is introduced to bind the primary antibody or the primary antibody-analyte complex. The signal of the fluorescent or chemiluminescent molecule is then detected. In other cases, the standard and / or one or more analytes can be detected via natural fluorescence (for example, via the fluorescence of the tryptophan amino acid in the standard and / or one or more analytes) and / or absorbance.

[0061] Then, the signal of the standard and the signal of one or more analytes can be compared to measure the concentration of one or more analytes in the sample.Additionally or alternatively, relevant characteristics of the analyte (e.g., isoelectric point, molecular weight, etc.) can be determined by comparison with the standard.

[0062] In certain embodiments, the internal standard can be the analyte itself in pure form, which is usually distinguishable from the analyte in some way. Any method for obtaining the analyte in pure form may include, but is not limited to, purification from nature, purification from an organism grown in a laboratory (e.g., via chemical synthesis), and / or similar methods. The distinguishing feature of the internal standard can be any appropriate change, which may include but is not limited to dye labeling, radioactive labeling, or modifying the mobility of the standard during electrophoretic separation so that the standard can be distinguishable from the analyte. For example, the analyte and the internal standard can each be labeled with a fluorescent dye, each of which can be detected at a discrete emission wavelength, thereby allowing the analyte and the standard to be independently detectable. In some cases, the internal standard is different from the analyte, but behaves in a similar or identical manner to the analyte, enabling relevant comparative measurements. In certain embodiments, standards suitable for use may be any of those described in U.S. Patent Application Publication No. 2007 / 0062813, filed September 20, 2006, entitled “Electrophoresis Standards, Methods and Kits,” the entire contents of which are hereby incorporated by reference herein.

[0063] In some cases, multiple analytes are detected and characterized from a single sample in a single capillary by the equipment, system and method provided herein. For example, in certain embodiments, multiple analytes are protein groups or protein subgroups. In this regard, it would be impractical to include a single internal standard corresponding to each of the individual proteins of the protein groups or protein subgroups. Therefore, in certain embodiments, a general isoelectric point standard is introduced into the system and equipment provided herein. In certain embodiments, the standard is a step standard that is operable to identify different isoelectric points along the capillary. The protein in the sample that migrates during electrophoresis is compared with the ladder to determine the isoelectric point of the protein present in the sample. In certain embodiments, a step standard is used.

[0064] In certain embodiments, above-mentioned analyte and / or standard are separated by any suitable mobility parameter, for example, charge, molecular weight, electrophoretic mobility (for example, affected by molecular weight, characteristic length, area or volume, oligonucleotide length or other suitable characteristic) and / or analog.For example, in certain embodiments, based on the mobility parameter such as isoelectric point or analog, sample is subjected to electrophoretic separation in the capillary comprising separation matrix.The capillary can include separation matrix, and it can be added in an automatic manner.In certain embodiments, separation matrix is ​​isoelectric separation matrix, and has similar or substantially the same property as the polymer gel used in traditional electrophoresis experiments, for example, pH gradient.The capillary electrophoresis in separation matrix is ​​similar to the separation in polymer gel, and the polymer gel is for example polyacrylamide gel or agarose gel, wherein by providing the porous path that can be passed through for molecule, molecule is separated based on the mobility parameter of the molecule in sample.

[0065] In certain embodiments, once separation is complete, the components of the separated sample (e.g., including analytes and / or standards) can be fixed to one or more walls of the capillary using any appropriate method, including, but not limited to, chemical, photochemical, and thermal treatment. In certain embodiments, the components of the separated sample are fixed in a fluid path (e.g., a fluid path defined by a capillary or the like) after the molecules have been separated by electrophoresis. For example, in certain embodiments, fixation occurs by subjecting the separated sample and the capillary to ultraviolet (UV) light, which is used to fix one or more analytes (if present in the sample) and molecules in the sample to the wall of the capillary. Fixation can be achieved via covalent bonds or via non-covalent means such as by hydrophobic or ionic interactions. In another embodiment, a reactive portion can be used to covalently fix one or more decomposed analytes in the fluid path. The reactive portion can be attached directly or indirectly to the fluid path (e.g., on one or more walls of the capillary). In certain embodiments, the reactive moieties may be supplied in a solution or suspension and may be configured to form bridges between the walls of the fluid path and molecules in the sample upon activation. The reactive moieties may be arranged in rows in the fluid path or may be present in the fluid path on linear or cross-linked polymers that may or may not be linked to the walls of the fluid path before and / or after activation. The reactive moieties may be and / or may include any reactive groups capable of forming covalent bonds with corresponding reactive groups of individual molecules of the sample, such as those described above.

[0066] In certain embodiments, the reactive part includes a functional group, which can be converted to the functionality of adhering to the analyte via hydrophobic interaction, ionic interaction, hydrogen bonding, etc. In certain embodiments, such reactive parts can be activated by UV light, laser, temperature or any other energy source, so that the analyte is fixed to the surface of the fluid path and / or fixed to the surface of the particles attached to the surface of the fluid path. In certain embodiments, the surface of the fluid path is functionalized by means of a thermoresponsive polymer, which changes the hydrophobicity of the surface when the temperature is changed. In certain embodiments, the analyte is fixed on such a surface by increasing the hydrophobicity of the temperature-responsive polymer when a certain temperature is reached in the fluid path. In yet other embodiments, the analyte can be probed and / or detected without first being fixed to the surface of the fluid path. For example, the analyte can be separated based on the isoelectric point (e.g., via isoelectric focusing), and at least as long as the sample in the fluid path is subjected to electric current, the analyte is maintained at their corresponding isoelectric point. In other words, once the analytes and / or standards are separated, the devices and / or systems described herein can continue to provide a flow of electrical current that is operable to maintain the analytes and / or standards at their respective isoelectric points (eg, fixed).

[0067] The fixed and / or otherwise separated analyte and / or standard are then probed for one or more probes and detected by means of one or more probes. The probe can be bound to or interact with the analyte and / or standard to be detected. The probe allows detection of standards and analytes by any means, such as but not limited to one or more fluorescent dyes, one or more optical dyes, one or more chemiluminescent reagents, radioactivity, particles, one or more magnetic particles, one or more paramagnetic particles, etc. The probe can include any organic or inorganic molecule, such as, proteins, peptides, antibodies, enzyme substrates, transition state analogs, cofactors, nucleotides, polynucleotides, nucleic acid aptamers, lectins, small molecules, ligands, inhibitors, drugs and other biomolecules and non-biological molecules capable of binding the analyte to be detected. In certain embodiments, the probe includes one or more label parts (as described above). In certain embodiments, the probe includes one or more label parts. In embodiments employing two or more label parts, each label part can be the same, or some or all of the label parts can be different.

[0068] In certain embodiments, the probe is used as a secondary reagent. For example, in certain embodiments, the probe is designed to bind to a first molecule, which is introduced to bind to an analyte and / or a standard, or to a complex of a first molecule and an analyte and / or a standard. For example, in certain embodiments, a "primary" monoclonal or polyclonal antibody is first introduced into a capillary comprising a fixed sample. The "primary" antibody binds to the analyte of interest (if present in the sample) and the free primary antibody is washed away. Next, a "secondary" antibody is introduced, which is designed to bind to the primary antibody or to span the region of the primary antibody-analyte complex. The secondary antibody includes a label portion for detecting the presence / absence of an analyte of interest and / or visualizing the presence / absence of an analyte of interest.

[0069] In certain embodiments, multiple immunoassays are performed in the apparatus and systems provided herein to detect the presence or absence of two or more analytes of interest (e.g., two, three, four, or five analytes) in a sample or to quantify the amount of two or more analytes in a sample. In yet another embodiment, the probe is the same for each of the analytes of interest. For example, the probe for each analyte is a secondary antibody coupled to a chemiluminescent label such as horseradish peroxidase. Differentiation between analytes occurs by initially introducing different primary antibodies into the capillary, each of which is specifically used for a unique analyte of interest.

[0070] The label portion coupled to the secondary antibody can be any appropriate label. For example, a general label can include an optical dye (e.g., a colored dye or a fluorescent dye); a chemiluminescent label, a phosphorescent label, an enzyme label (e.g., alkaline phosphatase and / or horseradish peroxidase), a bioluminescent label, an isotope label (e.g., a radioisotope or a heavy isotope), a mass label and / or a particle label (e.g., a colloid, a magnetic particle, etc.). In certain embodiments, the label portion is a chemiluminescent portion. In another embodiment, the chemiluminescent portion is horseradish peroxidase (HRP). In certain embodiments, HRP is coupled to a secondary antibody and used in an immunoassay to detect one or more analytes in a sample. In certain embodiments, the label portion can be a single isomeric dye. In certain embodiments, the label portion can be a fluorescent dye, which can include any entity that provides a fluorescent signal. For example, a fluorescent dye can include a resonance delocalized system or an aromatic ring system that absorbs light of a first wavelength and emits fluorescence of a second wavelength in response to an absorption event. The fluorescent dye can be any of various classes of fluorescent compounds, for example, xanthenes, rhodamines, fluoresceins, cyanines, phthalocyanines, squarylium cyanines, fluoroboron fluorescent dyes, coumarins, oxazine dyes and carbon red. In certain embodiments, the fluorescent dye is 5-carboxytetramethylrhodamine (5-TAMRA) and / or any other suitable class of fluorescent compounds.

[0071] In certain embodiments, the label portion may be and / or may include a chemiluminescent label. Suitable label portions may include such an enzyme, that is, the enzyme is capable of reacting with a chemiluminescent substrate in a manner that induces photon emission through chemiluminescence. For example, an enzyme may induce chemiluminescence in other molecules through enzymatic activity. Such an enzyme may be and / or may include a peroxidase, such as horseradish peroxidase (HRP), beta-galactosidase, phosphatase, and the like. In certain embodiments, the chemiluminescent label may be selected from any of various classes of luminol labels, isoluminol labels, and the like. In certain embodiments, the probe may include an antibody to a chemiluminescent label, such as a secondary antibody covalently bound to HRP. In certain embodiments, the probe includes a chemiluminescent substrate, such as a Galacton substrate available from Applied Biosystems of Foster City, California, or a SuperSignal West Femto Maximum Sensitivity substrate available from Pierce Biotechnology of Rockford, Illinois, or any other suitable substrate. In certain embodiments, the probe may be any of those described in U.S. Patent Nos. 6,689,576, 6,395,503, 6,087,188, 6,287,767, 6,165,800, and 6,126,870, the entire disclosures of which are hereby incorporated by reference herein.

[0072] In certain embodiments, the tag moiety can be and / or can include a bioluminescent compound (e.g., found in biological systems where a catalytic protein increases the efficiency of a chemiluminescent reaction). The presence of the bioluminescent compound is determined by detecting the presence of luminescence. Suitable bioluminescent compounds include, but are not limited to, luciferin, luciferase, and aequorin.

[0073] In certain embodiments, the tag moiety may be and / or may include a fluorescent dye. Such a fluorescent dye may include a resonant delocalized system or an aromatic ring system that absorbs light of a first wavelength and emits fluorescence of a second wavelength in response to an absorption event. The fluorescent dye may be any of various classes of fluorescent compounds, such as, but not limited to, xanthenes, rhodamines, fluoresceins, cyanines, phthalocyanines, squarylium cyanines, fluoroboron fluorescent dyes, coumarins, oxazine dyes, and carbon red. In certain embodiments, such as where the probe contains fluorescein such as a fluorescent dye, the fluorescence of the probe is detected by exciting the probe with an appropriate light source and by monitoring their fluorescence by a detector that is sensitive to the characteristic fluorescence emission wavelength of the probe.

[0074] As previously described, in certain embodiments, two or more different agents can be used to bind to or interact with two or more different analytes to enable simultaneous detection of more than one type of analyte. In certain embodiments, two or more different probes that bind to or interact with an analyte can be detected simultaneously. In various embodiments, using two or more different probes, one agent, such as a first primary antibody, can bind to or interact with one or more analytes to form a first agent-analyte complex, and a second agent, such as a secondary antibody, can be used to bind to or interact with the first agent-analyte complex.

[0075] In another embodiment, two different probes, such as antibodies for phosphorus-containing and non-phosphorus-containing forms of the analyte of interest, can achieve detection of two forms of the analyte of interest. In certain embodiments, a single specific probe, such as an antibody, can allow detection and analysis of both phosphorylated and non-phosphorylated forms of the analyte. In certain embodiments, multiple probes can be used for multiple substrates to provide color multiplexing. For example, different chemiluminescent substrates can be used to emit photons of different colors. Selective detection of different colors (e.g., via a diffraction grating, one or more prisms, a series of color filters and / or the like) can allow determination of which color of photons are emitted at any position along a fluid path (e.g., along a molecular weight gradient), and therefore determine which probe is present at each emission position. In certain embodiments, different chemiluminescent reagents can be supplied sequentially, allowing sequential detection of different bound probes.

[0076] Typically, during the standard immunoassay process performed in the apparatus and system described herein, a portion of the internal standard will be lost due to various cleaning processes. Thus, it is generally desirable to load a sufficient amount of internal standard in the sample at the start of the assay so that sufficient signals can be generated by the internal standard retained in the capillary after the immunoassay to provide coordination to calibrate the curve and analyze the molecular weight and / or individuality (e.g., number of amino acids or number of oligonucleotide base pairs) of the analyte. However, if the standard and the analyte are located in the same position, a larger amount of internal standard can interact with the capture of the analyte. As such, some standards are not arranged together with the analyte during and / or at the end of electrophoresis. However, such standards do not produce a reliable calibration curve for detecting the analyte. Therefore, in certain embodiments, the sample may include more than one standard. For example, the internal standard may be formed by a first standard (referred to as a "bright standard" or "registration standard") and a second standard (referred to as a "fuzzy standard") and / or include a first standard and a second standard. A bright standard may be a standard having a feature different from that of the analyte (e.g., isoelectric point). As such, after electrophoresis, the locations of the registered standard and the analyte are located far from each other in the capillary. Thus, the fluorescence emitted from the bright standard and the analyte will not overlap and do not interact with each other. The dim standard can be a standard having characteristics similar to those of the analyte (e.g., isoelectric point). As such, after electrophoresis, the locations of the registered standard and the analyte are located close to each other in the capillary.

[0077] The bright standard can be located at a position different from the position of the analyte along the flow path (e.g., a flow path defined by a capillary or the like) and provide coordination (e.g., an anchor point) for locating the fuzzy standard at a position close to the analyte or at the same position as the analyte, thereby providing an accurate calibration curve. Typically, the bright standard produces a brighter fluorescence than the fluorescence emitted by the fuzzy standard after the internal standard and the analyte have been separated. The difference in brightness between the bright standard and the fuzzy standard can be attributed to the difference in the nature of the emission and / or the difference in the amount of the two standards contained in the internal standard. For example, a larger amount of a bright standard and a smaller amount of a fuzzy standard can be mixed to form a standard that can produce a "bright" signal from the bright standard and a "fuzzy" signal from the fuzzy standard. Thus, the "bright" signal generated by the bright standard and the "fuzzy" signal generated by the fuzzy signal are detected after the separation step performed by electrophoresis. In certain embodiments, internal standards may include bright and dim standards such as those described in US Patent Application Publication No. 2011 / 0011740, the entire disclosure of which is hereby incorporated by reference herein.

[0078] Embodiments described herein can be used to facilitate one or more analyses of one or more analytes in a single system before visualizing and detecting analytes in samples (e.g., via molecular weight analysis and / or isoelectric focusing). Embodiments described herein can provide the functionality of a pipette and a microfluidic path, thereby enabling the analysis of very small volumes of samples. Such equipment and / or systems can include any suitable device, mechanism, assembly, subassembly, electronic device, actuator and / or the like, which can enable the equipment and / or system to, for example, separate, fix and / or detect any suitable target analyte. More specifically, the equipment and systems described herein are configured to receive a box including one or more capillaries and expose at least a portion of the box to a negative pressure difference (e.g., a negative pressure difference generated by a vacuum source), the negative pressure difference being operable to draw a volume of fluid (e.g., one or more reagents, samples, buffers, detergents, detection substances, analytes, amphoteric electrolytes and / or the like) from one or more wells or trays contained in the equipment and / or system into one or more capillaries of the box.

[0079] In certain embodiments, this box can have at least one capillary, and the at least one capillary is fixedly connected to the box body. One or more capillaries (for simplicity, the following relates to the singular) are configured to be placed in fluid communication with one or more fluid reservoirs (for example, arranged in the box body and / or arranged in a reagent tray or the like or limited by a reagent tray or the like). In certain embodiments, one or more fluid reservoirs can be holes or the like that contain fluid, and the fluid has such a composition, that is, the composition has any one of the above-mentioned chemical compositions. In certain embodiments, at least part of the box can be conductive (for example, formed by copper, platinum, stainless steel, conductive microplate plastics, carbon-impregnated plastics, conductive polymers and / or any other suitable materials). In certain embodiments, these parts of the box can have a volume resistivity less than 25 ohm*cm (ohm.cm) and a surface resistivity of 1000 ohms (or 1 kilo-ohm (kΩ) to 100kΩ. In other embodiments, the box and / or its parts are substantially non-conductive.

[0080] The capillaries of the cartridge define a lumen that receives at least a portion of a sample, solution, reagent, analyte, and / or any other suitable fluid or gel. The capillaries may be of any suitable shape, size, or configuration and may be made of any suitable material (e.g., glass, plastic, silicone, fused silica, gel, PYREX®, or a combination thereof) that allows liquids and / or dissolved molecules to flow through the lumen. TM(amorphous glass) and / or the like). For example, in some embodiments, the length of the capillary can be based at least in part on factors such as the degree of sample separation or sample size (e.g., between about 2 centimeters (cm) and about 20 cm) when decomposing one or more analytes of interest, wherein longer capillaries can facilitate separation of larger samples, which in turn can improve the resolution of complex mixtures and / or mixtures with lower abundance analytes. In some embodiments, the capillary of the box can be an elongated member having a full round or circular cross-sectional shape or a polygonal cross-sectional shape (e.g., trapezoidal, rectangular, square, pentagonal, octagonal, etc.). In some embodiments, the shape and / or size of the lumen defined by the capillary can be based at least in part on the type of sample, sample volume, and / or analysis (e.g., an inner diameter of about 10 thousandths of a millimeter or "micrometer" (μm) to about 1000 μm). For example, a capillary having a smaller inner diameter can be associated with a lower sample volume and / or otherwise used for a lower sample volume, which can be suitable for expensive samples or reagents. Conversely, a capillary defining a larger inner diameter may be associated with and / or otherwise used for higher sample volumes, which in some cases may result in improved signal detection or the like. In other embodiments, the inner diameter may be based at least in part on the analysis to be performed (e.g., molecular weight-based separation, isoelectric focusing, etc.).

[0081] Figure 11 is a schematic diagram of a portion of a system 1000 according to an embodiment configured to perform capillary electrophoresis (e.g., based on molecular weight and / or isoelectric point). For example, in some cases, a user may load a capillary cartridge into the system 1000 and may initiate instructions to the system 1000 and / or otherwise provide instructions to the system 1000 to cause the system to at least semi-automatically separate analytes (e.g., proteins) within a sample by molecular weight. In this case, the system 1000 captures a digital or analog image associated with the detection of an analyte within a sample (e.g., including any appropriate agent, reagent, protein, analyte, buffer, lysate, etc.) drawn into a capillary of the capillary cartridge. As such, the system 1000 may analyze images and / or other data associated with the detection and may provide molecular weight and / or morphological data of components of the sample. In other cases, a user may load a capillary cartridge into the system 1000 and may initiate instructions to the system 1000 and / or otherwise provide instructions to the system 1000 to cause the system 1000 to at least semi-automatically separate analytes within a sample by isoelectric point. In this case, the system 1000 draws a sample (e.g., including any suitable agents, reagents, proteins, analytes, buffers, lysates, etc.) into the capillary, separates and / or focuses the analytes in the sample within the capillary, and detects the presence or absence of a target analyte and / or detects the location of an analyte within the sample (e.g., an analyte that has migrated to a different location along the capillary associated with its isoelectric point). Optionally, the system 1000 can fix at least some components of the sample within the capillary (e.g., via heat, UV exposure, and / or the like) prior to detecting the target analyte.

[0082] like Figure 1 As shown in FIG. 1 , system 1000 includes housing 1100 , reagent tray assembly 1300 , capillary cartridge holder 1400 , and detection assembly 1700 . Figure 1 1000, but in certain embodiments, the system 1000 may include any suitable electronic system or component having at least a power source, a processor, and a memory that may be configured and / or otherwise programmed to perform one or more processes associated with performing at least semi-automated electrophoretic separation (e.g., a hardware module and / or a software module stored in the memory and executed in the processor). Similarly, the system 1000 may include any suitable fluid flow system or component that defines one or more fluid flow paths that are configured to receive fluids that may flow through the system 1000, e.g., a sample, one or more reagents, air, and / or the like, as described in further detail herein with reference to specific embodiments.

[0083] As described above, system 1000 is configured to receive capillary box 1500 (also referred to herein as "box"). Box 1500 may include at least body portion 1510, which is fixedly connected to at least one capillary 1530. Box 1500 may be of any appropriate shape, size or configuration. In certain embodiments, box 1500 may be associated with a specific analysis and / or otherwise configured for a specific analysis. For example, in certain cases, system 1000 may receive a box configured for molecular weight analysis. In other cases, system 1000 may receive a box configured for isoelectric focusing. In certain embodiments, box 1500 may have a size, shape and / or configuration that makes the box suitable for any analysis. In addition, box 1500 may include any appropriate identification mark, code and / or device, which may be automatically detected by system 1000 as the user positions box 1500 in system 1000.

[0084] The housing 1100 of the system 1000 may be of any suitable shape, size, or configuration, and may be arranged to at least partially enclose or at least partially contain any suitable components of the system 1000. For example, the housing 1100 may at least partially enclose the reagent tray assembly 1300, the capillary cartridge holder 1400, and the detection assembly 1700. Figure 1 In some embodiments, the housing 1100 may be configured to form one or more parts, chambers, internal volumes, etc., which are configured to allow at least some of the components of the system 1000 to be arranged therein. In some embodiments, the housing 1100 may include a door, which is configured to provide access to the internal volume thus defined. For example, a user may open the door of the housing 1100 to position the capillary box 1500 in the capillary box holder 1400, as described in further detail herein. In some embodiments, at least part of the housing 1100 may be lightproof, so that no large amount of light leaks through the housing into the chamber defined by the housing. In some embodiments, the housing 1100 may define at least one climate-controlled chamber. Similarly, the system 1000 may be operable to maintain the chamber of the housing at a constant and / or preset temperature, humidity, and / or other environmental parameters (e.g., illumination, etc.).

[0085] The capillary cartridge holder 1400 (also referred to herein as a "cartridge holder") is fixedly disposed within the housing 1100. For example, in certain embodiments, the cartridge holder 1400 can be coupled to a frame or the like that maintains the cartridge holder 1400 in a substantially fixed position within the housing 1100. In certain embodiments, the cartridge holder 1400 can also be coupled to and / or otherwise disposed in a fixed position relative to the detection assembly 1700, as described in further detail herein.

[0086] Box holder 1400 can be any suitable shape, size or configuration.For example, box holder 1400 can comprise for example a group of sidewalls, and described group of sidewalls limits internal volume, and described internal volume is configured to receive at least the portion of capillary box 1500 (also referred to as " box " in this article).More specifically, box holder 1400 can have or limit the cross section of roughly C shape, and wherein at least one side of box holder 1400 is open basically.Like this, the user can insert box 1500 by the side that is open basically of box holder 1400, so that at least the portion of box 1500 is positioned in the internal volume.In certain embodiments, box holder 1400 can comprise latch mechanism, and it is suitable for forming friction fit, snap fit, threaded connection and / or the like with at least the portion of box 1500, so that box 1500 is connected to box holder 1400. In other words, when the cartridge 1500 is partially inserted into the interior volume, the cartridge holder 1400 is at least temporarily coupled to the cartridge 1500 to maintain the cartridge 1500 in a substantially fixed position relative to the cartridge holder 1400 .

[0087] The cartridge holder 1400 is configured to receive the cartridge 1500 in a predetermined orientation (e.g., only one orientation or manner). Figure 1 1 , but the cartridge holder 1400 may include any suitable alignment features or sensors configured to engage and / or sense portions of the cartridge 1500 as the cartridge 1500 is positioned within the cartridge holder 1400. More specifically, the cartridge holder 1400 may include, for example, any number of features (e.g., protrusions, openings, recesses, etc.), components, mechanisms, sensors, and / or the like, each of which engages and / or senses portions of the cartridge 1500 to ensure that the cartridge 1500 is retained within the cartridge holder 1400 at a desired location and / or in a desired orientation.

[0088] In certain embodiments, the cartridge holder 1400 may include and / or otherwise be coupled to any suitable assembly, mechanism, device, and / or the like that is configured to engage the cartridge 1500 to control, for example, the flow of a fluid through at least a portion of the cartridge 1500. For example, in certain embodiments, the cartridge holder 1400 may include and / or be coupled to a vacuum source or assembly that is configured to generate a negative pressure within a volume (e.g., a lumen of a capillary tube or the like) of the cartridge 1500. The vacuum source may be fluidly coupled to a portion of the cartridge holder 1400 via a port or the like that places the vacuum source in fluid communication with the cartridge when the cartridge 1500 is held by the cartridge holder 1400. In certain instances, the vacuum source may be activated (e.g., by a manual switch and / or by an electrical switch contained in an electrical circuit and controlled by a processor) to generate a negative pressure within the cartridge 1500, as described in detail below with reference to certain embodiments. In certain embodiments, the cartridge holder 1400 may include a device or mechanism configured to engage the cartridge 1500 to selectively restrict bulk fluid flow through portions of the cartridge 1500. For example, the cartridge holder 1400 may include an actuator or the like that is selectively placed in contact with a pinch valve or the like contained in the cartridge 1500 to restrict and / or substantially prevent bulk fluid flow through the lumen of, for example, a capillary contained in the capillary cartridge 1500.

[0089] The box holder 1400 may also include any number of electrical contacts or the like that are configured to electrically couple portions of the box 1500 to electrical or electronic components contained in the system 1000. For example, in some embodiments, the box holder 1400 includes one or more conductive contact members, clips, surfaces, etc. that contact associated conductive contact members, clips, surfaces, etc. of the box 1500 when the box 1500 is held in the box holder. In some embodiments, at least a portion of the box 1500 may be formed of a conductive material, such as stainless steel, conductive plastic, or the like. Thus, when the box 1500 is held in a desired position within the box holder 1400, one or more conductive members or the like of the box holder 1400 contact one or more predetermined conductive portions of the box 1500, which in turn places the box 1500 in electrical or electronic communication with the electrical and / or electronic components contained in the system 1000. For example, the cartridge holder 1400 may electrically connect the conductive capillary of the cartridge 1500 and / or the conductive fluid within the lumen of the capillary to electrical and / or electronic components of the system 1000 , as described in further detail herein.

[0090] The reagent tray assembly 1300 of the system 1000 may be of any suitable shape, size, or configuration and may be arranged to receive, hold, and / or store at least a portion of a reagent tray ( Figure 1 ). The reagent tray assembly 1300 can receive and / or include any suitable reagent tray ( Figure 1 1300). For example, the reagent tray can maintain and / or otherwise limit a group of holes, orifice plates, microplates, grooves and / or the like. Holes and / or micropores can be any appropriate size, and can be arranged along the surface of the reagent tray and / or otherwise limited by the surface of the reagent tray in any appropriate arrangement. Although the specific example of the reagent tray is described herein, the reagent tray assembly 1300 can be configured to receive and / or include a suitable reagent tray of any similar size and / or shape, which can limit any number and / or any arrangement of holes and / or micropores. The holes and / or micropores contained in or limited by the reagent tray can receive any appropriate volume of solution, fluid, gel, lysate, buffer, sample, analyte, ampholyte, medicament, reagent, protein, matrix and / or the like. In certain embodiments, holes and / or micropores can receive a vial or the like of any appropriate fluid that is accommodated with a volume. In certain embodiments, the reagent tray assembly 1300 and / or portions of the reagent tray assembly 1300 are electrically conductive and electrically coupled to electrical and / or electronic components contained in the system 1000. In such embodiments, the reagent tray and / or portions of the reagent tray may also be electrically conductive and may facilitate electrical connection to fluids disposed within the reagent tray by coupling the reagent tray to the reagent tray assembly 1300.

[0091] At least a portion of the reagent tray assembly 1300 is movably disposed within the housing 1100 and / or movably coupled to the housing 1100. For example, the reagent tray assembly 1300 may be movably coupled to one or more rails, racks, lead screws, sliders, pistons, and / or the like, which may be operable to move the reagent tray assembly 1300 relative to the housing 1100. The reagent tray assembly 1300 (or at least the reagent tray contained therein) may be moved in a direction closer to or further away from the cartridge holder 1400, such as in Figure 1Indicated by arrow AA. In other words, when box 1500 is held by box holder 1400, reagent tray assembly 1300 can move in a direction parallel to the axis defined by the capillary 1530 of box 1500. In addition, reagent tray assembly 1300 can move in one or more directions along the plane orthogonal to box holder 1400, as indicated by arrow BB. That is to say, when box 1500 is held by box holder 1400, reagent tray assembly 1300 (or at least reagent tray included therein) can move along the plane orthogonal to the axis defined by the capillary 1530 of box 1500. In other words, reagent tray assembly 1300 (or at least reagent tray included therein) can move in the housing 1100 relative to box holder 1400 along X direction (e.g., left or right), Y direction (e.g., up or down) and Z direction (e.g., front or back).

[0092] Thus, the reagent tray assembly 1300 is configured such that at least the reagent tray ( Figure 1 1500) is moved relative to the box 1500 held by the box holder 1400 to arrange at least the end portion of one or more capillaries 1530 of the box 1500 in the hole, micropore, vial and / or the like of the reagent tray. In addition, the reagent tray assembly 1300 can move at least the reagent tray relative to the box 1500 and / or the box holder 1400 through any suitable number of positions to place one or more capillaries 1530 in any one of the holes, micropores and / or vials contained in the reagent tray or any suitable combination thereof. Therefore, in the case where the capillary 1530 is fluidically connected to the vacuum source (as described above), a negative pressure can be generated in the capillary 1530, which is operable to draw a volume of fluid such as those described above from any suitable one or more holes of the reagent tray into the capillary 1530. Additionally or alternatively, the hole, micropore, vial, etc. can be inserted into the hole, micropore, vial, etc. via a pressure conduit ( Figure 1 1500 ) is fluidically coupled to a positive pressure source via a capillary 1530. Portions of the reagent tray assembly 1300, the capillary 1530, and / or the cartridge 1500 may be operable to seal a hole, microwell, vial, etc., to the cartridge 1500 such that a positive pressure may push fluid from the hole, microwell, vial, etc. into the capillary 1530.

[0093] The detection assembly 1700 of system 1000 is fixedly arranged in the housing 1100. As mentioned above, the detection assembly 1700 is also arranged in a predetermined and fixed position relative to the box holder 1400. For example, the detection assembly 1700 can be arranged in the housing 1100 so that the predetermined portion of the detection assembly 1700 is aligned with the desired position relative to the predetermined portion of the box holder 1400 and / or is otherwise arranged in the desired position. In certain embodiments, the detection assembly 1700 and / or the box holder 1400 can include any suitable adjustment mechanism or the like to ensure that the desired alignment between the detection assembly 1700 and the box holder 1400.

[0094] Detection assembly 1700 can be any suitable device, mechanism and / or assembly, which is configured to capture and / or detect digital or analog data (e.g., image) of, for example, analytes and / or standards and / or detect signals emitted by analytes and / or standards. For example, in certain embodiments, detection assembly 1700 includes a first emitter 1705, a second emitter 1751, a first detector 1728, and a second detector 1760. The first emitter 1705 of detection assembly 1700 can be any suitable device, member, mechanism, assembly and / or the like, which is configured to release energy (e.g., heat, photons, radiation, etc.). For example, in certain embodiments, the first emitter 1705 can be one or more LEDs, deuterium lamps, lasers, incandescent light sources, fluorescent light sources, or any other suitable light sources. In certain embodiments, the first emitter 1705 can be optically coupled to box holder 1400, box 1500, and / or capillary 1530 via one or more lenses, mirrors, prisms, optical fibers, and / or the like. The first emitter 1705 can be powered and / or excited to emit photons having, for example, a predetermined wavelength and / or wavelength range. In certain embodiments, the detection component 1700 can include one or more mirrors, lenses, filters, or the like that are configured to direct, focus, and / or convert the wavelength of the photons emitted by the first emitter 1705. For example, the detection component 1700 can include any suitable lens and / or filter (e.g., TAMRA filter) associated with chemiluminescence, fluorescence (e.g., natural fluorescence, fluorescence of a tag moiety, etc.), absorbance, and / or the like.

[0095] Similarly, the second emitter 1751 can be any suitable device, member, mechanism, assembly and / or the like that is configured to release energy in the form of photons, heat, radiation, etc. In some embodiments, the second emitter 1751 can be, for example, an array of LEDs and / or any of the light sources described with reference to the first emitter 1705. In some embodiments, the first emitter 1705 is configured to emit photons during, for example, molecular weight analysis, and the second emitter 1751 is configured to emit photons during, for example, isoelectric focusing. In such embodiments. The first emitter 1705 can be, for example, a single fiber output (e.g., a single focused beam), while the second emitter 1751 can be, for example, a fiber output, a grid array of LEDs, or the like (e.g., a light column instead of a single focused beam). In other embodiments, a single emitter can be used during molecular weight analysis and isoelectric focusing (e.g., via one or more apertures, filters, blockers, reflectors, and / or refractors, etc.). In yet other embodiments, the detection assembly 1700 can include more than the first emitter 1705 and the second emitter 1751. As described in further detail herein, the first emitter 1705 (or multiple emitters) and the second emitter 1751 (or multiple emitters) can emit energy that interacts with at least a portion of the sample contained within the capillary 1530 of the cartridge 1500 when the cartridge 1500 is held by the cartridge holder 1400.

[0096] The first detector 1728 and the second detector 1760 can be any suitable digital or analog detector. For example, in certain embodiments, the first detector 1728 and / or the second detector 1760 can be and / or can include a photodiode, a photodiode array, a charge coupled device (CCD) array and / or the like. Detectors 1728 and 1760 can be used to capture images and / or signals associated with analytes and / or standards in a sample. In certain embodiments, detectors 1728 and 1760 can be operable to periodically and / or continuously capture images and / or signals emitted from analytes and / or standards. In certain embodiments, detectors 1728 and 1760 can be operable to monitor analytes and / or standards in real time or substantially in real time, which can allow a user to quickly determine whether there is an analyte in a sample, the amount of an analyte or the activity of an analyte, the molecular weight of an analyte and / or the like. In certain embodiments, for example, when the box 1500 is held by the box holder 1400, the first detector 1728 can be used to detect and / or image the sample flow through the capillary 1530 of the box 1500 in substantially real time during molecular weight analysis (in this case, the box 1500 is configured for molecular weight analysis). In certain embodiments, the second detector 1760 can be used during and / or after isoelectric focusing. For example, the second detector 1760 can be used to detect the separation of analytes in substantially real time when the analytes are separated and focused and / or after the analytes have been focused and optionally fixed. Similarly stated, when the box 1500 is held by the box holder 1400, the second detector 1760 detects a signal (e.g., fluorescence, absorbance, etc.) associated with one or more analytes contained in the sample, which have been separated in the capillary 1530 of the box 1500 (in this case, the box 1500 is configured for isoelectric focusing). In addition, detection component 1700 can be operably coupled to any appropriate electrical or electronic circuit and configured to send and / or receive signals from a processor or the like (e.g., detection component 1700 can send one or more signals to a processor or the like to cause data associated with the captured image and / or detected signal to be stored, for example, in a memory or database). Although detection component 1700 is described as including first detector 1728 and second detector 1760, in other embodiments, detection component 1700 can include a single detector or multiple detectors (e.g., more than two) configured to detect a portion of the energy (e.g., photons) generated by emitters 1705 and / or 1751.

[0097] In use, for example, system 1000 can be set, programmed and / or otherwise placed in a configuration to perform molecular weight analysis of a sample, which can include, for example, preparing a sample and / or reagents and preparing box 1500. Then, the user can insert box 1500 into box holder 1400 in a single predetermined orientation, as described above. Then, box holder 1400 is at least temporarily coupled to box 1500 to keep box 1500 in a substantially fixed position. The arrangement of box holder 1400 and detection assembly 1700 in housing 1100 makes a predetermined portion of detection assembly 1700 (e.g., first emitter 1705 and first detector 1728) align with a predetermined portion of box holder 1400 (e.g., first opening group or the like). Thus, by aligning the detection assembly 1700 with the cartridge holder 1400 and having the cartridge holder 1400 hold the cartridge 1500 in a predetermined fixed position, the first emitter 1705 and the first detector 1728 can be aligned with, for example, a portion of the capillary 1530 of the cartridge 1500. Thus, the energy and / or photons emitted by the first emitter 1705 can be directed to a predetermined portion of the capillary 1530.

[0098] As described above, the box 1500 (e.g., including the capillary 1530) is fluidly coupled to the vacuum source when positioned in the box holder 1400. Therefore, the vacuum source can then be activated (e.g., at least semi-automatically) to generate a negative pressure differential in the capillary 1530, which is operable to draw a substantially continuous sample flow through the capillary 1530. In this way, with the sample flowing through the capillary 1530, the first emitter 1705 can emit energy or photons, which in turn illuminate and / or excite a volume of the sample flowing through a predetermined portion of the capillary 1530 (where the energy or photons are directed). The first detector 1728 can then capture and / or detect one or more images, image data, and / or signals associated with the illuminated and / or excited analyte, standard, etc. within the volume of the sample. Additionally or alternatively, the first detector 1728 can capture and / or detect one or more images, image data, and / or signals associated with light absorbed by the analyte, standard, etc. The images and / or data may then be analyzed to determine molecular weight-based data, electrophoretic mobility, size-based data, and / or morphological data associated with the analytes in the sample.

[0099] In a similar manner, the system 1000 can be configured, programmed, and / or otherwise placed in a configuration so that when the cartridge 1500 is held by the cartridge holder 1400, capillary electrophoresis is performed and / or signals of one or more analytes contained in the sample that have been separated and / or focused within the capillary 1530 of the cartridge 1500 (in this case, the cartridge 1500 is configured for isoelectric focusing). In this case, a user can insert the cartridge 1500 (in this case, the cartridge 1500 is configured for isoelectric focusing) into the cartridge holder 1400 in a single predetermined orientation, as described above. Thus, by aligning the detection assembly 1700 with the cartridge holder 1400 (e.g., such that the second emitter 1751 and the second detector 1760 are aligned with, for example, the second opening group) and having the cartridge holder 1400 hold the cartridge 1500 in a predetermined fixed position, the second emitter 1751 and the second detector 1760 can be aligned with, for example, a portion of the capillary 1530 of the cartridge 1500. Thus, the second emitter 1751 can emit energy or photons that are directed to a predetermined portion of the capillary 1530 (e.g., a predetermined length or corresponding column of the capillary 1530).

[0100] In some cases, the second emitter 1751 and the second detector 1760 can collectively capture a "full column" image and / or perform a "full column" detection of a sample within the capillary 1530. Similarly stated, the second emitter 1751 and the second detector 1760 can be operable to capture and / or detect more than one single point along the capillary 1530. For example, the second emitter 1751 and the second detector 1760 can be operable to capture a sufficient length to visualize the separation and / or focusing of the analyte during the electrophoresis process. The second emitter 1751, the second detector 1760, and optional additional optical components can be operable to define an optical path of the capillary 1350 having a length of about 1 cm, about 3 cm, about 5 cm, about 10 cm, about 20 cm, about 50 cm, or any other suitable length. Additionally or alternatively, the second emitter 1751 and the second detector 1760 may be operable to capture natural fluorescence, label fluorescence, and / or absorbance of an analyte, standard, etc., within the capillary 1530. For example, a filter wheel ( Figure 1 1530) can be operable to alter the optical signal presented to the second detector 1760 while the analytes are separated and / or focused within the capillary 1530. Thus, during a single run, a sample can be characterized for native fluorescence, tag fluorescence, absorbance, and / or any other suitable optical characteristic along the entire column while the analytes are separated and / or focused.

[0101] As described above, a volume of a mixture (e.g., one or more reagents, samples, buffers, detergents, detectors, analytes, ampholytes, antibodies, labels, and / or the like) can be drawn into the capillary 1530 in response to a negative pressure differential created by a vacuum source. However, where the system 1000 is configured to perform isoelectric focusing, once a desired volume of sample or other desired fluid is drawn into the capillary 1530, the cartridge holder 1400 and / or any other suitable portion of the system 1000 can engage a portion of the cartridge 1500, such as to switch a pinch valve or the like to a closed position, which in turn restricts and / or substantially prevents bulk fluid flow through the capillary 1530. Additionally, the system 1000 can apply an electric field to a conductive portion of the cartridge 1500 (e.g., the fluid within the capillary 1530 and / or the capillary 1530, as described above). Thus, an electric current can flow along the capillary 1530, and the separated analytes in the mixture are separated by the isoelectric point gradient (e.g., along the length of each capillary). Optionally, in some embodiments, once the molecules are sufficiently separated and / or focused, the system 1000 can be configured to fix the molecules within the capillaries of the box 1500. For example, the second emitter 1751 can emit energy or photons (e.g., a light column or a fluorescent beam) that is directed to a predetermined portion of the capillary 1530 (e.g., a predetermined length or corresponding column of the capillary 1530) so that the volume of the separated sample or mixture within the corresponding column of the capillary 1530 is irradiated, excited, and fixed within the capillary 1530.

[0102] In the case where the sample components (e.g., containing one or more analytes) are separated, the separated one or more analytes and / or one or more standards contained in the sample are probed with one or more reagents, which may include detection agents (e.g., any suitable agent, reagent, analyte-specific antibody, HRP-conjugated secondary antibody and / or the like, or any combination thereof, as described in detail above). The detection reagent is then used to generate a signal from one or more labeling moieties (e.g., isotopic labels, immunolabels, optical dyes, enzymes, particles, or combinations of particles, e.g., chemiluminescent-tagged antibodies, fluorescent-tagged antibodies, and / or the like), which is then captured or detected by the second detector 1760. In other embodiments, the natural fluorescence and / or absorbance characteristics of the analyte can generate a signal captured by the second detector 1760. For example, an analyte (e.g., a protein and / or a portion of a protein, e.g., the constituent amino acid tryptophan) can be excited by the second emitter 1751 and detected by the second detector 1760. In other cases, a reduction in light emitted from the second emitter 1751 that is characteristic of an analyte absorbance peak can be detected by the second detector 1760. In this way, the system 1000 can be used to at least semi-automatically perform molecular weight analysis and / or isoelectric focusing.

[0103] Although described above as fixing molecules in a sample, in other embodiments, the system 1000 does not need to fix molecules within the sample. For example, after the sample is separated and / or focused, the first detector 1728 and / or the second detector 1760 can capture the final image of the capillary 1530, and / or the molecules in the sample can be detected before the sample is flushed into a waste container, and / or the sample is recaptured or otherwise disposed. In such an embodiment, the box 1500 can be reusable so that the same box 1500 and / or capillary 1530 can be used to separate and / or focus subsequent samples.

[0104] Figures 2 to 44 A system 2000 configured to perform capillary electrophoresis such as molecular weight and / or isoelectric focusing measurements is shown according to an embodiment. The system 2000 includes a housing 2100 and / or a support structure ( Figures 2 to 8 )、electronic components 2200( Figure 8 )、Reagent assembly 2300( Figures 9 to 13 )、Box holder 2400( Figures 14 to 20 ) and optical assembly 2700( Figures 20 to 28 ). System 2000 is configured to receive a cassette, for example, molecular weight cassette 2500' ( Figures 29 to 37 ) and / or isoelectric focusing box 2500" ( Figures 38 to 44 As described in further detail herein, system 2000 can at least semi-automatically characterize analytes within a sample by molecular weight and / or isoelectric point. System 200 can be operable to draw a sample (e.g., including any suitable agent, reagent, protein, analyte, buffer, lysate, and / or any other material described herein) into cartridges 2500' and / or 2500" (collectively referred to herein as "cartridges 2500" (see, e.g., Figure 7 )) and imaging a volume of sample as it flows through. In addition, system 2000 can at least semi-automatically separate samples (via capillary electrophoresis) and image the samples during and / or after separation, for example, via full-column detection.

[0105] like Figures 2 to 8 As shown in , the housing 2100 and / or support structure (hereinafter referred to as "housing") can be any suitable shape, size and / or configuration, and can be arranged to at least partially enclose or at least partially support any suitable components of the system 2000. The housing 2100 includes a cover 2110, a base 2112, a theater cover 2114, a frame 2120, a door 2130, and a door retaining assembly 2140. Figure 2As shown in , the cover 2110 is coupled to the base 2112 to collectively cover, contain, and / or otherwise enclose at least a portion of the system 2000 .

[0106] The door 2130 of the housing 2100 is coupled to the cover 2110 and / or portions of the frame 2120 and can be moved relative to the cover 2110 between a closed configuration and an open configuration to isolate or access portions of the system 2000 disposed within the cover 2110, respectively. Figure 3 and Figure 4 As shown in , the door 2130 of the housing 2100 includes a door frame 2131, a hinge 2132, a door cover 2133, a handle 2134, a latch 2135, a sensor 2136, and a sensor plate 2137. The door frame 2131 supports the door 2130 and provides structural rigidity for it. The hinge 2132 is connected to the door frame 2131 and a portion of the frame 2120 of the housing 2100. The hinge 2132 may include, for example, a first portion rotatably connected to a second portion. In this way, the first portion and / or the second portion can be configured to rotate and / or pivot around an axis (not shown) to allow the door 2130 to be in a closed configuration (e.g., Figure 5 ) and open configuration (e.g. Figure 6 )

[0107] The door cover 2133 is arranged around the door frame 2131. In some embodiments, the door cover 2133 can be opaque and configured to limit the amount of light allowed into the interior volume defined by the cover 2110. In other embodiments, the door cover 2133 can include a viewing window and / or the like, which is configured to allow a user to visualize the portion of the system 2000 disposed within the cover 2110. The handle 2133 of the door 2110 is operably coupled to the latch 2135 and can be manipulated by a user to convert the latch 2135 between a first configuration (e.g., a latched or locked configuration) and a second configuration (e.g., an unlatched or unlocked configuration). The latch 2135 is configured to selectively engage the door retention assembly 2140 to selectively prevent the door 2130 from moving relative to the cover 2110. The sensor 2136 is configured to sense and / or detect the relative position of the door 2130, as described in further detail herein.

[0108] For example, as in Figure 6 and Figure 7As shown in , the door holding assembly 2140 includes a release mechanism 2141 and one or more actuators 2142. The release mechanism 2141 is configured to selectively engage the latch 2135 of the door 2130 to selectively hold the latch 2135 in a fixed position (e.g., at least temporarily hold the door 2130 in a closed configuration). The actuator 2142 can be any suitable actuator or the like that is configured to convert the release mechanism 2141 between a first configuration in which the release mechanism 2141 engages the latch 2135 and a second configuration in which the release mechanism 2141 is disengaged from the latch 2135. For example, in some embodiments, the actuator 2142 can be an electromechanical actuator or the like that is configured to mechanically move a portion of the release mechanism 2141 in response to a signal or instruction received, for example, from the electronic assembly 2200 or other controller.

[0109] The door retention assembly 2140 also includes one or more proximity sensors 2143 configured to detect the relative position of the door 2130. For example, in some embodiments, the one or more proximity sensors 2143 can be configured to detect proximity to and / or contact with a portion of the sensor plate 2137 of the door 2130. In this way, the sensor 2136 of the door 2130 and the proximity sensor 2143 of the door retention assembly 2140 can collectively sense and / or detect the position and / or configuration of the door 2130 relative to, for example, the lid 2110 and / or other portions of the housing 2100. In addition, in some cases, the sensors 2136 and / or 2143 can be configured to send a signal to, for example, the electronic assembly 2200 and / or other control devices associated with the position and / or configuration of the door 2130, which in turn can activate portions of the system 2100 (e.g., when the door 2130 is in a closed configuration) and / or prevent portions of the system 2100 from being activated (e.g., when the door 2130 is in an open configuration).

[0110] Frame 2120 is configured to support one or more portions of system 2100. For example, frame 2120 includes: at least one optical support member 2121 configured to support at least a portion of optical assembly 2700; and electronic assembly support member 2122 configured to support at least a portion of electronic assembly 2200 and / or optical assembly 2700. Theater cover 2114 is coupled to frame 2120 and is configured to at least partially isolate portions of system 2100 (see, e.g., Figure 6 and Figure 7 ). In certain embodiments, the theater cover 2114 can be a shield or the like that is configured to block, limit, and / or substantially prevent portions of the system 2000 from being undesirably exposed to light (eg, from outside the cover 2110).

[0111] Electronic assembly 2200 may be of any suitable configuration and may include any suitable components to enable electronic assembly 2200 to at least partially control system 2000. For example, Figure 8 As shown in , electronic assembly 2200 includes at least power supply 2210, printed circuit board assembly (PCBA) 2212, and one or more fans 2215 configured to cool components of electronic assembly 2200. As described in further detail herein, PCBA 2212 is in electrical communication with one or more system components, such as pumps, lights, cameras, detectors, motors, sensors, auxiliary PCBAs, and / or any other suitable devices. Although in Figure 8 2210 can be electrically connected to an external circuit (e.g., "plugged in") to receive electrical current from a power grid. In turn, the power supply 2210 can condition, transform, and / or convert the electrical current (e.g., from alternating current (AC) to direct current (DC)) before being transmitted to the electronic PCBA 2212. In addition, the power supply 2210 can be configured to provide electrical current to one or more pumps, motors, actuators, lights, detectors, cameras, sensors, and / or the like, as described in further detail herein.

[0112] PCBA 2212 may include any suitable electronic device or component. For example, PCBA 2212 includes at least a memory and a processor (not shown). The memory may be, for example, a random access memory (RAM), a storage buffer, a hard drive, a read-only memory (ROM), an erasable programmable read-only memory (EPROM), and / or the like. In some embodiments, the memory may store instructions to cause the processor to execute modules, processes, and / or functions associated with at least part of the control system 2000. The processor may be any suitable processing device that can run and / or execute a set of instructions or codes. For example, the processor may be a general-purpose processor, a central processing unit (CPU), an accelerated processing unit (APU), an application-specific integrated circuit (ASIC), and / or the like. The processor may run and / or execute a set of instructions or codes stored in the memory that are associated with at least part of the control system 2000. For example, the processor may execute a set of instructions or codes stored in the memory that are associated with controlling one or more pumps, motors, actuators, sensors, lights, cameras, and the like. In addition, the processor can execute a set of instructions or codes stored in the memory associated with sending current to portions of the cartridge assembly 2500 to initiate and / or perform electrophoresis, as described in further detail herein.

[0113] like Figures 9 to 13As shown in , the reagent assembly 2300 of the system 2000 includes at least a drive portion 2310 and a tray portion 2340. The drive portion 2310 is configured to move the tray portion 2340 of the reagent assembly 2300 in response to one or more signals received from, for example, the electronic assembly 2200. Fig.10 and Fig.11 As shown in , the drive portion 2310 includes a first motor 2311 coupled to a first drive screw 2312, a second motor 2315 coupled to a second drive screw 2316, and a third motor 2320 coupled to a third drive screw 2321. The drive portion 2310 also includes a first slide 2313, a second slide 2317, and a third slide 2322. The first motor 2311 is fixedly coupled to a base plate 2113, which in turn is coupled to a portion of the frame 2120 to support at least the drive portion 2310 of the reagent assembly 2300. In other words, the first motor 2311 is coupled to the base plate 2113 and maintained in a substantially fixed position.

[0114] Although in Figures 9 to 13 23. Although not shown, the first slide rail 2313 is configured to slidably receive a slider. For example, in some embodiments, the first slide rail 2313 may include one or more grooves, channels, slots, tracks, etc., which are configured to receive and / or slidably engage a portion of a slider (not shown). The slider is then connected to the slide plate 2318. In other embodiments, the slider and the slide plate 2318 are formed integrally or unitarily. In addition, the slide plate 2318 is connected to the end portion of the first drive screw 2312. For example, in some embodiments, the slide plate 2318 may include and / or may be connected to (e.g., via one or more mechanical connectors, welding, adhesives and / or the like) a mounting plate or bracket, which in turn forms a threaded connection with the first drive screw 2312. Thus, when the first motor 2311 is actuated, the output of the first motor 2311 causes the first drive screw 2312 to rotate relative to the mounting plate or bracket of the skateboard 2318, and thereby causes the skateboard 2318 to move in a linear direction (e.g., closer to or farther away from the first motor 2311) along the length of the first slide rail 2312, as further described in detail herein.

[0115] The second motor 2315 and the second slide rail 2317 of the drive portion 2310 are both coupled to the slide plate 2318. More specifically, the second slide rail 2317 is coupled to and / or otherwise contained in the slide plate 2318, and the second slide rail 2317 extends along the length of the slide plate 2318 in a direction perpendicular to the first slide rail 2313. As described above with reference to the first slide rail 2313, the second slide rail 2317 is configured to slidably receive a slider (not shown), which in turn is coupled to the slide bracket 2323. The slide bracket 2323 is further coupled to an end portion of the second drive screw 2316. As such, when the second motor 2315 is actuated, the output of the second motor 2315 causes the second drive screw 2316 to rotate relative to the slide bracket 2323, and thereby causes the slide bracket 2323 to move in a linear direction (e.g., closer to or farther away from the second motor 2315) along the length of the second slide rail 2316, as described in further detail herein.

[0116] The third slide rail 2322 is coupled to the slide bracket 2323 and is configured to extend along the length of the slide bracket 2323 in a direction perpendicular to each of the first slide rail 2313 and the second slide rail 2316, as shown in FIG. Fig.10 and Fig.12 As described above with reference to the first rail 2313 and the second rail 2316, the third rail 2322 is configured to slidably receive the slider 2342 ( Fig.12 ), the slider 2342 is then coupled to the mounting plate 2344 of the tray portion 2340. The third motor 2320 is coupled to the motor mount 2345 of the mounting plate 2344, so that the end portion of the third drive screw 2321 extends through the motor mount 2345 to be rotatably coupled to the sliding bracket 2323. Fig.10 and Fig.11 , the third drive screw 2321 extends in a direction substantially parallel to the third slide rail 2322 (e.g., in a direction orthogonal to the base plate 2113 and / or in a direction perpendicular to both the first drive screw 2312 and the second drive screw 2316). When the third motor 2320 is actuated, the output of the third motor 2320 causes the third drive screw 2321 to rotate relative to the third motor 2320, and as such, the third motor 2320 moves along the length of the third drive screw 2321. Therefore, with the third motor 2320 coupled to the mounting plate 2344, the movement of the third motor 2320 along the length of the third drive screw 2321 causes the mounting plate 2344 (and the slider 2342) to move in a linear direction (e.g., closer to or further away from the slide plate 2318) along the length of the third slide rail 2322.

[0117] The arrangement of the drive portion 2310 is such that in response to one or more signals from the electronic component 2200, the drive portion 2310 can move the tray portion 2340 of the reagent component 2300 along a plane parallel to the substrate 2113 in any appropriate direction and in a direction perpendicular or orthogonal to the plane. In other words, the drive portion 2310 can move the tray portion 2340 in the X direction, the Y direction, and the Z direction. In addition, by connecting the second motor 2315 to the slide 2318, which is movably connected to the first slide rail 2313, and by connecting the third motor 2320 to the mounting plate 2344, which is movably connected (at least indirectly) to the second slide rail 2316 and the third slide rail 2322, the drive portion 2310 can be configured to simultaneously actuate the first motor 2311, the second motor 2315, and the third motor 2322 to move the tray portion 2340 in any appropriate direction within the XY plane, the XZ plane, and / or the YZ plane. Fig.10 and Fig.11 As shown in , the drive portion 2310 also includes a cable track 2325, which can receive one or more wires and / or conduits. In this way, one or more wires and / or conduits can move relative to the slide 2318 and the sliding bracket 2323 (for example, in the cable track 2325 and / or at the same time as the cable track 2325) in response to the actuation of the first motor 2311, the second motor 2315 and / or the third motor 2320.

[0118] The tray portion 2340 of the reagent assembly 2300 can be any suitable shape, size and / or configuration. Fig.12 , the tray portion 2340 includes a mounting plate 2344, a cooler 2350, a cooling block 2360, a tray support 2362, a reagent tray 2365, and a shield 2368. Each of the cooler 2350, the cooling block 2360, the reagent tray 2365, and the shield 2368 is coupled to the tray support 2362, which in turn is coupled to the mounting plate 2344 and / or otherwise supported by the mounting plate 2344. Thus, with the mounting plate 2334 coupled to the slider 2342 (as described above), the mounting plate 2344 and the slider 2342 slidably couple the tray portion 2340 of the reagent assembly 2300 to the drive portion 2310 of the reagent assembly 2300. In some embodiments, the drive portion 2310 can place the tray portion 2310 in a default position or otherwise in a predetermined position when the system 2000 is not in use and / or before or after moving the tray portion 2310. In some embodiments, the shield 2368 can be coupled to the tray holder 2362 such that at least a portion of the shield 2368 is substantially aligned with an associated portion of the theater cover 2114 (see, e.g., Figure 6). In this way, the shield 2368 and the theater cover 2114 can collectively isolate the portion of the system 2000 within the housing 2100.

[0119] Reagent tray 2365 is configured to be at least temporarily coupled to tray holder 2362. For example, reagent tray 2365 can be removably coupled to tray holder 2362, which can allow a user to remove and / or replace reagent tray 2365 (for example, for cleaning or similar treatment). Reagent tray 2365 can be coupled to tray holder 2362 so that the surface of reagent tray 2365 contacts the surface of cooling block 2360, as described in further detail herein. Reagent tray 2365 can be any suitable tray or the like. For example, reagent tray 2365 can support and / or otherwise limit a group of holes 2366, which is configured to receive any suitable solution, fluid, gel, lysate, buffer, sample, analyte, ampholyte, medicament, reagent, protein, matrix and / or the like. In other embodiments, hole 2366 can receive one or more vials 2367 or the like, which can accommodate any of sample and / or mixture described herein. The holes 2366 can be any suitable shape, size, or configuration and can be arranged in any suitable arrangement. For example, the holes 2366 can be a well plate, a microplate, and / or the like. Fig.12 , reagent tray 2365 includes 42 holes 2366. In other embodiments, reagent tray can include any number of holes (e.g., more than 42 holes or less than 42 holes). In certain embodiments, reagent tray 2365 is removably connected to tray support 2362 so that a reagent tray with holes of any appropriate number and / or arrangement can be at least temporarily connected to tray support 2362. In addition, the drive portion 2310 of reagent assembly 2300 can move tray portion 2340 in housing 2100, so that one or more holes 2366 of reagent tray 2365 can be selectively placed to be communicated with the part of box holder 2400 and / or the box 2500 fluid arranged in box holder 2400, as described in further detail herein.

[0120] The cooler 2350 of the tray portion 2340 is coupled to the tray support 2362. The cooler 2350 may be any suitable device, mechanism, assembly, and / or the like configured to transfer thermal energy to or from the cooler 2350. For example, Fig.12 As shown in , the cooler 2350 includes a fluid block 2351 and a thermoelectric cooling device 2355. The fluid block 2351 has an inlet 2352 and an outlet 2353, wherein the inlet 2352 is configured to receive an inlet fluid flowing into the fluid block 2351, and the outlet 2353 is configured to receive an outlet fluid from the fluid block 2351. Fig.13 As shown in , the fluid block 2351 is fluidly coupled to a pump 2385, which in turn is fluidly coupled to a heat exchanger 2390 (e.g., a shell and tube heat exchanger, a radiator, and / or the like). In this way, the pump 2385 can receive a flow of a hotter or heated fluid (e.g., water, a coolant, and / or the like) from an outlet 2353 of the fluid block 2351, and can pump a volume of the fluid into the heat exchanger 2390. The heat exchanger 2390 includes and / or is coupled to a fan 2395, which is configured to supply a flow of a volume of fluid (e.g., air) across an outer surface of the heat exchanger 2390, thereby removing thermal energy from the fluid flowing within the heat exchanger 2390. The cooler or cooled fluid can then flow into the inlet 2352 of the fluid block 2351. In this way, the fluid flowing through the fluid block 2351 can be configured to transfer thermal energy from the fluid block 2351 or transfer thermal energy to the fluid block 2351.

[0121] Thermoelectric cooling device 2355 (also referred to herein as "cooling device") can be any suitable cooling device, for example, a Peltier device and / or similar device, which is configured to generate a temperature gradient in response to an electrical input (e.g., a voltage or voltage change). In certain embodiments, cooling device 2355 has a hot surface that is thermally connected to at least the fluid flowing through fluid block 2351 and a cold surface that is thermally connected to at least the cooling block 2360. In this way, cooling device 2355 can receive a flow of electric current (e.g., from power supply 2210 of electronic assembly 2200), which is operable to generate a temperature gradient between the cold surface and the hot surface of cooling device 2355. Therefore, in the case where cooling block 2360 is in contact with reagent tray 2365 (as described above), thermal energy can be transferred from reagent tray 2365 to the cold surface of cooling device 2355 via cooling block 2360, and transferred to the fluid flowing in fluid block 2351 by cooling device 2355. Then, as the fluid flows through the heat exchanger 2390, at least a portion of the heat energy is removed from the fluid, as described above. Thus, the tray portion 2340 of the reagent assembly 2300 can cool, refrigerate and / or otherwise condition the sample and / or other mixture within the reagent tray 2365.

[0122] Alternatively, the hot surface of the cooling device 2355 can be thermally connected to the cooling block 2360, and the cold surface of the cooling device 2355 can be thermally connected to the fluid through the fluid block 2351, so that the cooling device can be operated to transfer heat energy to the reagent tray 2365 (for example, it can be operated to be used as a heater). For example, by changing the polarity of the voltage applied to the cooling device 2355, the cooling device 2355 can be operated to alternate between the heating device and the cooling device. In some cases, a controller such as a proportional-integral-differential (PID) controller can be operable to change polarity, duty cycle, duration, potential, etc., which is supplied to the cooling device 2355 to maintain the temperature of the reagent tray 2365 within a specific temperature range. In certain embodiments, such a controller can be and / or can include a set of instructions stored in a memory and executed in a processor of the PCBA 2212 of the electronic assembly 2200.

[0123] The capillary cartridge holder 2400 (also referred to herein as a "cartridge holder") of the system 2000 is disposed within the housing 2100. For example, Fig.14 , a portion of the cartridge holder 2400 is fixedly coupled to the optical support member 2121 of the frame 2120. As such, at least a portion of the cartridge holder 2400 is maintained in a substantially fixed position within the housing 2100. More specifically, a portion of the cartridge holder 2400 is coupled to the optical support member 2121 and maintained in a fixed position relative to the detection assembly 2700, thereby maintaining a desired alignment between the optical support member 2121 and the detection assembly 2700, as described in further detail herein.

[0124] The cartridge holder 2400 may be of any suitable shape, size or configuration. Figures 15 to 20 As shown in , the cartridge holder 2400 includes a frame 2410, a vacuum portion 2440, a latch mechanism 2455, and a pipette portion 2470. As described in further detail herein, the frame 2410 is configured to couple the cartridge holder 2400 to the optical support member 2121 and to receive and selectively engage at least a portion of the cartridge 2500. In addition, as shown in Figures 15 to 18 As shown in , each of the vacuum portion 2440 , the latch mechanism 2455 , and the pipette portion 2470 are coupled to and / or otherwise supported by the frame 2410 .

[0125] like Fig.15 and Fig.16, the pipette portion 2470 is coupled to a side wall of the frame 2410 (e.g., the second side wall 2421, as described in further detail herein) and includes a pipette 2481 configured to move in a linear direction relative to the frame 2410. The pipette portion 2470 also includes a mounting block 2471, a motor 2472, a rack 2473, a pinion 2474, a belt 2475, a support member 2476, a slide rail 2478, and a slider 2479. The mounting block 2471 and the support member 2476 are each configured to be coupled to the second side wall 2421 of the frame 2410. The motor 2472 is coupled to the mounting block 2471 and includes an output (not shown). The output of the motor 2472 is operably coupled to the pinion 2474 via the belt 2475. Pinion 2474 is rotatably coupled to mounting block 2471 and is configured to be rotated by belt 2475 in response to rotation of the output of motor 2472. Rack 2473 is configured to engage a gear or the like (not shown) of pinion 2474 to move in a linear motion relative to mounting block 2471. Fig.16 , the end portion of the rack 2473 and the pipette 2481 are coupled to a slider 2479. The slider 2479 is slidably disposed around a portion of a slide rail 2478, which in turn is configured to be coupled to a support member 2476 and maintained in a substantially fixed position relative to the frame 2410. In addition, the support member 2476 defines a notch 2477 that is configured to movably receive a portion of the latch mechanism 2455, as described in further detail herein.

[0126] This arrangement of the pipette portion 2470 is such that when the motor 2472 is actuated, the belt 2475 rotates the pinion 2474 relative to the rack 2473. With the pinion 2474 rotatably coupled to the mounting block 2471 and with the gear portion of the pinion 2474 meshing with the rack 2473, the rotation of the pinion 2474 advances the rack 2473 relative to the pinion 2474. With the end portion of the rack 2473 coupled to the slider 2479, the advancement of the rack 2473 relative to the pinion 2474 causes the slider 2479 to move linearly along the length of the slide 2478. Thus, with the pipette 2481 coupled to the slider 2479, the pipette 2481 moves simultaneously with the slider 2479 as the slider 2479 moves along the length of the slide 2478. In this way, the electronic assembly 2200 can send a signal and / or power to the motor 2472 to move the pipette 2481 in a linear direction along the length of the slide 2478 (e.g., along the length of the centerline defined by the pipette 2481).

[0127] In some cases, the pipette 2481 can be moved from a first position to a second position to be placed in one or more holes 2366 of the reagent tray 2365. For example, in some cases, the motor 2472 can be actuated (e.g., in response to a signal and / or power received from the electronic assembly 2200) to position the first end portion of the pipette 2481 in the hole 2366 of the reagent tray 2465. In addition, as Fig.16 , a second end portion of the pipette 2481 opposite the first end portion is in fluid communication with at least one fluid conduit 2480. Thus, the pipette 2481 can be configured to deliver fluid to and / or receive fluid from the aperture 2366 within which the fluid is disposed. For example, in some embodiments, one or more fluid conduits 2480 are in fluid communication with a pump 2490 or the like (see, e.g., Fig.13 ). The pump 2490 is also in fluid communication with at least one fluid reservoir 2495. Thus, the electronic assembly 2200 and / or other control device can send a signal to the pipette assembly 2470 to actuate the motor 2472 so that the first end portion of the pipette 2481 is placed in the desired hole 2366. The electronic assembly 2200 can also send a signal to the pump 2490 (e.g., a syringe pump or other suitable pump), and in response, the pump 2490 can draw a predetermined volume of fluid from one or more fluid reservoirs 2495 and can deliver the predetermined volume of fluid to the hole 2366 via one or more fluid conduits 2480 and the pipette 2481. In certain embodiments, this arrangement can enable the system 2000 to at least semi-automatically fill and / or otherwise prepare one or more holes 2366 of the reagent tray 2365 with a desired sample or mixture (e.g., those described herein).

[0128] In some embodiments, the size of one or more fluid reservoirs 2495 can be set to accommodate a smaller amount of fluid, for example, 20 milliliters (mL), 50 milliliters, 100 milliliters, etc. One or more fluid reservoirs 2495 can store a certain amount of fluid sufficient for a single or a number of times (e.g., 2 times, 5 times, 10 times, etc.) operation. In some cases, the interior of the housing 2100 can be climate controlled so that one or more fluid reservoirs 2495 are maintained at a preset and / or substantially constant temperature. For example, fans 2215 and / or 2395 can be circulated so that such heat generated from system components (e.g., electrical components, power supplies, transformers, cooling devices 2355, etc.) is discharged at a controlled rate to maintain a preset and / or substantially constant temperature. The size of one or more fluid reservoirs 2495 can be set to accommodate a smaller amount of fluid, the temperature of which can be more easily controlled than, for example, a large number of fluid reservoirs of multiple liters.

[0129] In some cases, one or more fluid reservoirs 2495 can be fluidly coupled to one or more bulk fluid containers (not shown) located, for example, outside the housing 2100. One or more fluid reservoirs 2495 can be operable to draw and / or otherwise receive fluid from one or more bulk fluid containers. In some embodiments, the filling level of one or more bulk fluid containers with known volumes can be determined by supplying a known amount of gas to one or more bulk fluid containers at a known pressure. By calculating the pressure change in one or more bulk fluid containers, the volume of the headspace can be determined (e.g., in one or more fluid reservoirs 2495 and / or in one or more bulk fluid containers). That is, as the headspace increases, the pressure change in the bulk fluid container decreases. The filling level can be calculated by subtracting the headspace from one or more bulk fluid containers of known volume. In some embodiments, when the filling level drops below a predetermined level and / or otherwise modifies the operating behavior, the system 2000 can prompt the user to refill one or more bulk fluid containers (e.g., the system 2000 can prevent the execution of the assay until one or more bulk fluid containers are refilled).

[0130] The frame 2410 of the cartridge holder 2400 may be of any suitable shape, size and / or configuration. Figures 16 to 19 As shown in , the frame 2410 includes a first side wall 2411, a second side wall 2421, a first contact bracket 2438 (e.g., an upper contact bracket), and a second contact bracket 2489 (e.g., a lower contact bracket). The first contact bracket 2438 and the second contact bracket 2439 are both arranged between the first side wall 2411 and the second side wall 2421, and are configured to be coupled to the first side wall 2411 and the second side wall 2421. More specifically, the first contact bracket 2438 and the second contact bracket 2439 are coupled to and arranged between the first side wall 2411 and the second side wall 2421, so that the side walls 2411 and 2421 are spaced apart by a predetermined distance (see, e.g., Fig.19 ). In some embodiments, the predetermined distance can be associated with, for example, the width of the box 2500. In other words, the first contact bracket 2438 and the second contact bracket 2439 couple the side walls 2411 and 2421 together so that a space sufficient to receive at least a portion of the box 2500 is defined therebetween. As described in further detail herein, each of the first contact bracket 2438 and the second contact bracket 2439 is coupled to a contact member 2485 that is positioned to contact a portion of the box 2500 when the box 2500 is disposed between the second side wall 2421 and the first side wall 2411.

[0131] like Fig.17As shown in the figure, the first side wall 2411 defines one or more spring openings 2412, a first optical opening 2414, and a second optical opening 2415. The first optical opening 2414 is configured to be aligned with a first portion of the optical assembly 2700 (e.g., the size imaging portion 2701, as described in further detail herein) to allow a user to visualize the first portion of the cartridge 2500 when the cartridge 2500 is held by the cartridge holder 2400. Similarly, the second optical opening 2415 is configured to be aligned with a second portion of the optical assembly 2700 (e.g., the full column detection portion 2750, as described in further detail herein) to allow a user to visualize the second portion of the cartridge 2500 when the cartridge 2500 is held by the cartridge holder 2400.

[0132] One or more spring openings 2412 defined by the first side wall 2411 are configured to receive portions of the spring 2450. For example, Fig.17 , first sidewall 2411 defines two spring openings 2412, and the two spring openings 2412 receive the different parts of spring 2450. Spring 2450 (for example, leaf spring or the like) can be a thinner elongated member, which can be bent, deformed, biased and / or otherwise reconfigured, and in response, a reaction force can be applied. Like this, the part of spring 2450 can be arranged in spring opening 2412, so that spring 2450 is placed in a biased configuration, and the biased configuration is configured to convert potential energy into kinetic energy in response to the force applied on at least part of spring 2450. As shown in the figure, spring 2450 includes a roller 2451 arranged at the end portion of spring 2450, and the roller 2451 is placed in contact with the surface of box 2500 as box 2500 is inserted into the box retainer 2400. In some embodiments, when the cartridge 2500 is placed in contact with the roller 2451 , the cartridge 2500 exerts a force on the spring 2450 sufficient to bias or temporarily deform the spring 2450 .

[0133] like Fig.18 and Fig.19As shown in the figure, the second side wall 2421 has an inner surface 2427, which includes and / or forms a first guide 2428 (e.g., an upper guide) and a second guide 2429 (e.g., a lower guide). The first guide 2428 and the second guide 2429 are configured to selectively engage, guide and / or support relevant portions of the box 2500 when the box 2500 is arranged in the space defined between the first side wall 2411 and the second side wall 2421. More specifically, the first guide 2428 and the second guide 2429 can engage and / or guide portions of the box 2500 to ensure that the box 2500 is held in the box holder 2400 at a desired position and / or in a desired orientation. For example, in some embodiments, the alignment of the box 2500 in the box holder can have a tolerance of 1.0 micrometer (μm) to about 500 μm (0.5 millimeter (mm)) or less.

[0134] As described in further detail herein, the second sidewall 2421 defines a latch opening 2422, a vacuum motor opening 2423, a first optical opening 2424, a second optical opening 2425, and a recess 2426. The recess 2426 defined by the second sidewall 2421 is configured to receive and / or otherwise be disposed around a portion of the optical support member 2121 of the frame 2120 to facilitate coupling of the cartridge holder 2400 to the optical support member 2121. The latch opening 2422 and the vacuum motor opening 2423 are configured to receive a portion of the latch mechanism 2455 and a portion of the vacuum motor 2447, respectively. As described above with reference to the first side wall 2411, the first optical opening 2424 and the second optical opening 2425 of the second side wall 2421 are configured to align with the first portion and the second portion of the optical assembly 2700, respectively, to allow for visualization of the first portion and / or the second portion, respectively, of the cartridge 2500 when the cartridge 2500 is held by the cartridge holder 2400. Additionally, at least the second optical opening 2425 may include and / or may receive the focusing lens 2405 and / or any other suitable optical component.

[0135] The second sidewall 2421 also includes and / or is coupled to a shaft 2430 and a coupling member 2431. The shaft 2430 is an elongated member having a first end portion and a second end portion opposite to the first end portion, wherein the first end portion is movably coupled to the second sidewall 2421 and / or movably arranged in the second sidewall 2421, and the second end portion is coupled to the coupling member 2431. The shaft 2430 is configured to move relative to the second sidewall 2421 in response to an applied force. For example, in certain embodiments, the reagent tray 2365 can move in a vertical direction so that a portion of the reagent tray 2365 and / or a sample vial contained therein is placed in contact with the coupling member 2431. In this way, the further movement (in the same direction) of the reagent tray 2365 applies a force to the coupling member 2431, which is sufficient to move the shaft relative to the second sidewall 2421 in a vertical direction. More specifically, in certain embodiments, a portion of the shaft 2430 is movably arranged in an opening defined by the second sidewall 2421. In such embodiments, the force exerted on the engagement member 2431 may be sufficient to increase the portion of the shaft 2430 disposed in the opening, thereby compressing and / or otherwise reducing the length of the shaft 2430 extending from the second sidewall 2421. In certain embodiments, the arrangement of the shaft 2430 and the engagement member 2431 may be configured to limit the movement of the reagent tray 2365 in the vertical direction to substantially prevent damage to the box 2500 and / or the box holder 2400 that may otherwise result from the absence of the box 2500 and / or the box holder 2400. In other embodiments, the shaft 2430 and / or the engagement member 2431 may include and / or may be operably coupled to a sensor or the like (e.g., a proximity sensor, a pressure sensor, an accelerometer, and / or the like) that is configured to sense and / or detect a position and / or force associated with the movement of the shaft 2430 (and / or the reagent tray 2365) relative to the box holder 2400. Thus, based at least in part on data sensed and / or determined by such a sensor, the system 2000 can control movement of the reagent tray 2365 and / or any other appropriate portion of the system 2000 relative to the box holder 2400.

[0136] As described above, the vacuum portion 2440 and the latch mechanism 2455 are coupled to the frame 2410. Figures 16 to 19 As shown in FIG. 2 , the vacuum portion 2440 of the cartridge holder 2400 includes a lever arm 2441, a pinch valve actuator 2444, a pressure nozzle 2445, a motor 2447, and a vacuum port 2448. The lever arm 2441 has a first end portion 2442 and a second end portion 2443. The first end portion 2442 of the lever arm 2441 is rotatably coupled to the second side wall 2421 of the frame 2410, for example, via a bearing or a pin (see, e.g., FIG. 2443 ). Fig.17). The second end portion 2443 of the lever arm 2441 is coupled to a connector 2446 or the like that is configured to connect and / or couple the second end portion 2443 of the lever arm 2441 to the motor 2447. More specifically, the motor 2447 is coupled to the second side wall 2421 of the frame 2410 such that an output member or the like extends through the vacuum motor opening 2423 (see, e.g. Fig.18 ) and is coupled to connector 2446. Thus, connector 2446 operably couples lever arm 2441 to motor 2447. As such, motor 2447 can rotate its output in response to a signal and / or power (e.g., sent from electronics assembly 2200), which in turn causes lever arm 2441 to rotate and / or pivot about an axis defined by first end portion 2442 (e.g., about a pin, axle, pivot point, etc.).

[0137] The pinch valve actuator 2444 and the pressure nozzle 2445 are both coupled to the lever arm 2441 and are configured to move with the lever arm 2441 in response to actuation of the motor 2447. More specifically, the pinch valve actuator 2444 is coupled to and / or otherwise disposed at or near the second end portion 2443 of the lever arm 2441 while the pressure nozzle 2445 is disposed closer to and / or substantially at the center portion of the lever arm 2441. As described in further detail herein, the pinch valve actuator 2444 and the pressure nozzle 2445 are each configured to selectively engage a predetermined portion of the cartridge 2500 when the cartridge 2500 is held by the cartridge holder 2400 and the motor 2447 is actuated to rotate the lever arm 2441. For example, in certain embodiments, the pinch valve actuator 2444 can be configured to actuate a pinch valve included in the cartridge 2500 to control fluid flow through one or more fluid flow paths. Similarly, the pressure nozzle 2445 can be configured to engage and / or actuate a portion of the box 2500 that is configured to regulate the pressure within one or more fluid flow paths and / or capillaries. For example, the pressure nozzle 2445 can be fluidically coupled to a pump 2497 or the like (e.g., via any appropriate fluid conduit, tubing, pipeline, and / or the like), which can be actuated to generate a positive pressure. In this way, the pressure nozzle 2445 can engage a portion of the box 2500 to transfer at least a portion of the positive pressure to the portion of the box 2500, as described in further detail herein.

[0138] like Fig.17 and Fig.19, the vacuum port 2448 is coupled to the first contact bracket 2438. As described in further detail herein, the vacuum port 2448 is configured to engage and / or contact a portion of the cartridge 2500 when the cartridge 2500 is disposed within the cartridge holder 2400. Although not shown, the vacuum port 2448 may be coupled to any suitable fluid conduit, tubing, pipe, and / or the like, which in turn places the vacuum port 2448 in fluid communication with a vacuum source. For example, a fluid conduit or the like may be configured to place the vacuum port 2448 in fluid communication with a vacuum source 2496 (see, e.g., Fig.13 ). The vacuum source 2496 can be any suitable device and / or the like that is configured to create a negative pressure differential between the vacuum source 2496 and, for example, the vacuum port 2448. In some embodiments, the vacuum source 2496 can include an impeller or the like that is configured to swirl within the chamber to create a negative pressure. In other embodiments, the vacuum source 2496 can be a piston pump or other suitable pump. In this way, the vacuum source 2496 can be activated (e.g., in response to a signal and / or power received from the electronic assembly 2200) to create a negative pressure within a portion of the cartridge 2500 when the cartridge 2500 is in contact with the vacuum port 2448, as described in further detail herein.

[0139] The latch mechanism 2455 of the cartridge holder 2400 may be any suitable member, device, mechanism and / or assembly. Fig.16 , Fig.18 and Fig.19 As shown in , the latch mechanism 2455 includes a latch arm 2456, a motor 2459, and a manual release member 2465. The latch arm 2456 can be of any suitable shape, size, and / or configuration. The first end portion of the latch arm 2456 is configured to be coupled to an output (not shown) of the motor 2459 such that rotation of the output causes a similar and / or corresponding rotation of the latch arm 2456. Fig.18 and Fig.19 , the latch arm 2456 includes a pin 2457 and a latch member 2458. The pin 2457 is configured to be placed in contact with a stop and / or portion of the frame 2410 to limit the rotation of the latch 2456. The latch member 2458 is coupled to an end portion of the latch arm 2456 opposite the end portion coupled to the motor 2459. The latch member 2458 can be any suitable pin, roller, knob, tab, protrusion, etc., which is configured to selectively engage a portion of the cartridge 2500 when the cartridge 2500 is disposed within the cartridge holder 2400, as described in further detail herein.

[0140] The latching member 2458 may be operable to securely position the cartridge 2500 on the first contact bracket 2438 and the second contact bracket 2439 with a high degree of accuracy and repeatability. Thus, as the cartridge 2500 is inserted into the cartridge holder 2400, the latching member 2458, the guide rails 2428 and 2429, and the contact brackets 2438 and 2439 may collectively align the cartridge 2500. In some cases, it may be desirable to closely control the insertion direction (e.g., insertion of the cartridge 2500 into the cartridge holder 2400) and / or alignment of the cartridge 2500 to ensure that the cartridge 2500 is aligned with the optical assembly 2700. In some cases, the latching member 2458, the guide rails 2428 and 2429, and the contact brackets 2438 and 2439 may be operable to reproducibly position the cartridge 2500 within a tolerance of, for example, 0.1 mm, 0.05 mm, 0.01 mm, 0.005 mm, or any other suitable distance. In addition, the cartridge holder 2400 may include one or more sensors 2488 (see, e.g., Fig.19 ), which is configured to detect and / or sense the position or alignment of the cartridge 2500 within the cartridge holder 2400. For example, the sensor 2488 can be a proximity sensor and / or any suitable switch, plunger, actuator (e.g., mechanical and / or electrical), etc. In certain embodiments, the sensor 2488 can send a signal to the motor 2459 indicating an instruction to rotate the latch arm 2456 when the cartridge 2500 is placed in a desired position within the cartridge holder 2400.

[0141] The manual release member 2465 includes a first end portion 2466, a second end portion 2467, and a contact portion 2468. The first end portion 2466 of the manual release member 2465 is rotatably coupled to the second side wall 2421 of the frame 2410, as shown in FIG. Fig.18. In addition, a portion of the manual release member 2465 is movably disposed within a recess 2477 defined by the support member 2476. The second end portion 2467 is opposite to the first end portion 2466 and can be engaged and / or manipulated by a user to pivot and / or rotate the manual release member 2465 around an axis (e.g., a pin, screw, axle, coupler, bearing, etc.) defined by the first end portion 2466. In addition, when the manual release member 2465 is rotated around the axis defined by the first end portion 2466, the contact portion 2468 is placed in contact with the pin 2457 of the latch arm 2456. In this way, the user can apply a force on the second end portion 2467 of the manual release member 2465 to place the contact portion 2468 in contact with the pin 2457 of the latch arm 2456, which in turn can rotate and / or pivot the latch arm 2456 relative to the frame 2410. Thus, if the motor 2459 and / or the like fails, the cartridge 2500 may be manually released from the cartridge holder 2400 .

[0142] The optical assembly 2700 of the system 2000 is disposed within the housing 2100 and coupled to the optical support member 2121 of the frame 2120. More specifically, the optical assembly 2700 may be disposed within the housing 2100 to at least partially surround the cartridge holder 2400. Figures 20 to 28 As shown in FIG. 2 , the optical assembly 2700 includes a single point detection portion 2701 ( Figure 20 to Figure 23 ) and full column detection section 2750 ( Figure 24 to Figure 28 ). The single point detection portion 2701 may be of any suitable shape, size and / or configuration. Fig. 20 As shown in , the single point detection portion 2701 is coupled to the box holder 2400 in a predetermined position and / or is otherwise arranged around the box holder 2400 so that one or more components of the single point detection portion 2701 are substantially aligned with the first optical opening 2414 of the first side wall 2411 and the first optical opening 2424 of the second side wall 2421, respectively, so as to enable the single point detection portion 2701 to perform a molecular weight analysis on a sample or the like flowing through the box 2500 (e.g., molecular weight box 2500'). As further described in detail herein, the full column detection portion 2750 is arranged around the box holder 2400 in a predetermined position so that one or more components of the full column detection portion 2750 are substantially aligned with the second optical opening 2415 of the first side wall 2411 and the second optical opening 2425 of the second side wall 2421, respectively, so as to enable the full column detection portion 2750 ...) before, during and / or after separation (see, e.g., Fig.24 ) detects the movement of an analyte (e.g., a protein) along the length of a capillary 2500 (e.g., an isoelectric focusing cell 3500").

[0143] like Figure 21 to Figure 23 , the single point detection portion 2701 includes an illumination assembly 2705, a center member 2710, a first side member 2720 coupled to a first imaging device 2725, and a second side member 2730 coupled to a second imaging device 2735. In addition, the single point detection portion 2701 can include any number of filters, lenses, holders, mirrors, and / or the like configured to direct at least a portion of the light emitted from the illumination assembly 2705, as described in further detail herein.

[0144] The illumination assembly 2705 includes an entry block 2706 and a fiber optic member 2707 (also referred to herein as an "optical output"). The entry block 2706 is coupled to a side of the central member 2710 and is further coupled to the optical output 2707. In this way, the entry block 2706 can direct and / or guide a light beam (e.g., photons) emitted from the optical output 2707 into one or more bores defined by the central member 2710, as described in further detail herein. The optical output 2707 can be optically coupled to a light source 2795 (see, e.g., Fig.13 ), for example, a deuterium lamp, an incandescent lamp, an LED, or any suitable fiber optic light source, and / or the like, which can be energized or otherwise activated in response to a signal and / or power received from the electronics assembly 2200 (e.g., the power supply 2210) and / or any other suitable control device. In some embodiments, the optical output 2707 can be configured to emit energy and / or photons generated by the light source 2795 having a desired wavelength (e.g., a wavelength in the infrared spectrum, the visible spectrum, the ultraviolet spectrum, and / or the like).

[0145] The central member 2710 may be of any suitable shape, size and / or configuration. Fig. 22 and Fig.23 , the center member 2710 defines a center bore 2711, side bores 2712, a cartridge holder recess 2713, a mirror recess 2714, and a filter recess 2715. The center bore 2711 has a substantially circular cross-sectional shape and extends laterally across the length of the center member 2710. In this embodiment, the center bore 2711 receives, for example, three lenses 2741, a mirror 2742, and a filter holder 2743 that holds or includes a filter 2744. More specifically, the central bore 2711 has: a first lens 2741, which is arranged adjacent to the entrance block 2706 of the lighting assembly 2705; a second lens 2741, which is arranged adjacent to the first side of the box holder recess 2713 on a first side of the box holder recess 2713; and a third lens 2741, which is arranged adjacent to a second side of the box holder recess 2713, which is opposite to the first side, on a second side of the box holder recess 2713 (see, e.g. Fig.23). Mirror 2742 is arranged in mirror recess 2714, which places mirror 2742 in a desired position to direct at least a portion of the light emitted from optical output 2707 to side bore 2712, as described in further detail herein. Filter holder 2743 is arranged in filter recess 2715, which places filter 2744 (supported by and / or coupled to filter holder 2743) in a desired position between first lens 2741 and side bore 2712. In this way, first lens 2741 can focus at least a portion of the light emitted from optical output 2707, and in turn, filter 2744 can filter a portion of the light before the light enters the side bore 2712 and / or the remainder of central bore 2711 (see, e.g. Fig.23 ).

[0146] Return to reference Fig. 20 , the single point detection portion 2701 of the optical assembly 2700 is positioned relative to the cartridge holder 2400 such that at least a portion of the cartridge holder 2400 is disposed within a cartridge holder recess 2713 defined by the central member 2710. More specifically, the single point detection portion 2701 and the cartridge holder 2400 are collectively arranged such that a central bore 2711 of the central member 2710 is substantially aligned with portions of first optical openings 2414 and 2424 defined by first and second sidewalls 2411, 2424 of the frame 2410, respectively. As such, the lens 2741, filter 2744, and mirror 2742 disposed within the central bore 2711 collectively direct a focused and filtered portion of light emitted by the optical output 2707 through a predetermined portion of the cartridge holder 2400. Thus, when the cartridge 2500 is held by the cartridge holder 2400, the focused and filtered portion of light similarly passes through a predetermined portion of the cartridge 2500, as described in further detail herein.

[0147] The first side member 2720 of the single point detection portion 2701 defines a bore 2721 and a recess 2722. The first side member 2720 is coupled to the center member 2710 such that the bore 2721 of the first side member 2720 is substantially aligned with the side bore 2712 of the center member 2710. The bore 2721 of the first side member 2720 receives and / or houses a lens 2741. In this way, the mirror 2742 disposed in the center bore 2711 of the center member 2710 can direct at least a portion of the light emitted by the optical output 2707 into the bore 2721 of the first side member 2720, which is then focused by the lens 2741 disposed therein.

[0148] The first side member 2721 is also coupled to a first imaging device 2725 (see e.g. Fig.21). The first imaging device 2725 includes a thermal mass reference member 2726, an insulator 2727, and a photodiode printed circuit board assembly (PCBA) 2728. The thermal mass reference member 2726 is disposed in the insulator 2727, and the insulator 2727 isolates (e.g., thermally isolates) the thermal mass reference member 2726, such as Fig. 22 . Insulator 2727 and thermal mass reference member 2726 are arranged in recess 2722 defined by first side member 2722 (e.g., between first side member 2722 and photodiode PCBA 2728). Thermal mass reference member 2726 can be any suitable device, sensor and / or the like. Thermal mass reference member 2726 can be configured to maintain first imaging device 2725 at a substantially constant and / or reference temperature. Photodiode PCBA 2728 (also referred to herein as "photodiode") can be any suitable device configured to sense and / or detect input of light (e.g., photons) and convert the input into current. In this way, photodiode 2728 can generate a signal associated with the scattering of light emitted by optical output 2707 and / or an image of a volume of a sample flowing through the capillary of box 2500. Such a signal can be interpreted by a processor (e.g., a processor of electronic assembly 2200) to determine the characteristic molecular weight, electrophoretic mobility, morphology, etc. of an analyte within the sample. Although described as a photodiode, in other embodiments, the single point detection portion 2701 may include any suitable imaging device, such as a CCD camera or the like.

[0149] The second side member 2730 of the single point detection portion 2701 includes a mirror block 2740 configured to be coupled to and / or otherwise retain a mirror 2742 and define a bore 2731 and a recess 2732. The second side member 2730 is coupled to and / or disposed adjacent to the center member 2710. Fig.21 As shown in , the arrangement of the single point detection portion 2701 is such that the first side member 2720 is coupled to and / or disposed on a first side of the cartridge holder recess 2713 and the second side member 2730 is coupled to and / or disposed on a second side of the cartridge holder recess 2713 that is opposite to the first side. In addition, the second side member 2730 is positioned relative to the center member 2710 such that a portion of the light emitted from the optical output 2707 is redirected by the mirror 2742 into the bore 2731 defined by the second side member 2730, which is then focused by one or more lenses 2741 disposed within the bore 2731,

[0150] As described above with reference to the first side member 2720, the second side member 2730 is also coupled to a second imaging device 2735 (see, e.g., Fig.21 ). The second imaging device 2735 includes a thermal mass reference member 2736, an insulator 2737, and a photodiode PCBA 2738. The second imaging device 2735 may be substantially similar to the first imaging device 2725 described above, and therefore is not specifically described in detail herein.

[0151] The first imaging device 2725 and the second imaging device 2735 may individually and / or collectively generate signals (e.g., electronic signals including data and / or information) associated with the generation, scattering, and / or absorption of light in both the first imaging device 2725 and the second imaging device 2735 along a front-to-back direction affected by an analyte, a standard, a label portion, etc. in a volume of a sample flowing through the capillary of the cartridge 2500. For example, in some cases, the first imaging device 2725 may be operable to detect light emitted, scattered, and / or absorbed from a dark field and / or a rearward viewpoint (e.g., approximately 95 degrees to 265 degrees opposite to the direction of the light beam), while the second imaging device 2735 may be operable to detect light emitted, scattered, and / or absorbed from a bright field and / or a forward viewpoint (e.g., approximately 85 degrees to 275 degrees along the direction of the light beam). Like this, the single point detection part 2701 of system 2000 can be the part of the capillary of box 2500 that can be operated to detect when the analyte separated by for example molecular weight and / or electrophoretic mobility flows through, as described in further detail herein.The molecular weight of each analyte can be determined based on the time and / or order of detecting it.For example, the analyte detected after detecting the 10000Da standard but before detecting the 15000Da standard can be determined to have the molecular weight between 10000 and 15000.By taking into account the timing between detecting the 10000Da standard, the analyte and the 15000Da standard, the molecular weight can be determined more accurately.

[0152] The full column detection portion 2750 of the optical assembly 2700 can be any suitable device, mechanism, subassembly and / or the like. As described above with reference to the single point detection portion 2701, the optical assembly 2700 is arranged within the housing 2100 so that the full column detection portion 2750 surrounds at least a portion of the cartridge holder 2400. The full column detection portion 2750 and the single point detection portion 2701 of the optical assembly 2700 can both surround a portion of the cartridge holder 2400 so that either imaging mode can be used depending on, for example, the configuration of the cartridge 2500 inserted into the cartridge holder 2400, as described in further detail herein.

[0153] like Figure 24 to Figure 28As shown in FIG. 2 , the full-column detection portion 2750 includes an illumination assembly 2751, an imaging assembly 2760, and a focusing assembly 2770. The illumination assembly 2751 may be any suitable device and / or assembly configured to generate light energy output. For example, Fig.25 and Fig.26 As shown in , the lighting assembly 2751 includes a linear optical output array 2752, a mounting structure 2753, and a lens 2759. The linear optical output array 2752 (also referred to herein as an "optical output") can be any suitable emitter (e.g., a light or photon emitter). For example, in some embodiments, the optical output 2752 can be an optical fiber output array that is configured to emit light energy generated by a light source (e.g., light source 2795). In some embodiments, the optical output 2752 can be an LED array and / or the like. In still other embodiments, the optical output 2752 can be a single emitter that is configured to emit light through an elongated aperture or the like defined by the optical output 2752. In this way, the optical output 2752 can output, for example, a light column having a predetermined length.

[0154] In some embodiments, the optical output 2752 can output light energy and / or photographs having a wavelength in the ultraviolet spectrum or a similar spectrum. In some embodiments, the optical output 2752 can be a narrowband light source and / or can produce a light column having a single wavelength. In other embodiments, the optical output 2752 can include a filter or a monochromator configured to output a light column having a single wavelength. In this way, the optical output 2752 can emit photons having a desired wavelength and / or energy (e.g., ultraviolet wavelength or energy), which are absorbed by one or more analytes, standards, fluorescent tags or the like within the sample contained in the capillary of the box 2500. In addition, one or more analytes, standards, tags or the like can then emit one or more photons (e.g., via fluorescence, phosphorescence and / or the like), which are then detected by the imaging component 2760, as described in further detail herein.

[0155] In some cases, the optical output 2752 can be operable and / or optimized for full column and / or real-time detection. For example, the optical output 2752 can be an LED array configured to output a more constant optical output over a longer duration, as compared to, for example, a laser light source. More specifically, certain known electrophoresis methods use a laser to illuminate a single point on the column at a high intensity over a shorter duration. Such methods are suitable for delivering enough energy to a single point to achieve accurate measurement, but because the intensity of the laser can damage the detector if the laser is applied for a longer period of time, this method is generally not suitable for full column detection or real-time detection. However, an LED array can generate enough energy by illuminating the entire column at a lower intensity over a longer duration to achieve accurate measurement of the entire column while electrophoresis is occurring.

[0156] The mounting structure 2753 includes a first adjustment block 2754, a second adjustment block 2755, an adjustment plate 2756, and a pair of mounting fixtures 2758. The mounting fixtures 2758 are coupled to the end portions of the adjustment plate 2756 to clamp, couple, and / or otherwise maintain the lens 2759 in a fixed position relative to the end portions of the adjustment plate 2756, such as Fig.25 The mounting structure 2753 is configured to adjustably support and / or adjustably mount the optical output 2752 to, for example, an optical support plate 2121 of the frame 2120. More specifically, as Fig.26 As shown in FIG. 27 , the mounting structure 2753 includes a first mounting plate 2757 and a second mounting plate 2757, wherein the first mounting plate 2757 is configured to adjustably couple the first adjustment block 2754 to the second adjustment block 2755, and the second mounting plate 2757 is configured to adjustably couple the second adjustment block 2755 to the adjustment plate 2756. In certain embodiments, the mounting structure 2753 is arranged so that the first adjustment block 2754 allows for horizontal adjustment of at least a portion of the lighting assembly 2751 (e.g., relative to the box holder 2400) and the second adjustment block 2755 allows for vertical adjustment of at least a portion of the lighting assembly 2751 (e.g., relative to the box holder 2400). Similarly, the optical output 2752 can be slidably coupled to the adjustment plate 2756 so that the optical output 2752 can slide along the length of the adjustment plate 2756 to be positioned closer to or farther from, for example, the lens 2759. In this way, the optical output 2752 can be placed in a desired position relative to the box holder 2400 and / or the box 2500 held by the box holder 2400, as described in further detail herein.

[0157] The imaging assembly 2760 of the full-column detection portion 2750 may be and / or may include any suitable device, mechanism, assembly, and / or the like. Fig. 27 and Fig.28 As shown in , imaging assembly 2760 includes imaging device 2761, sealing bracket 2762, one or more seals 2763, rotating flange 2765 and transition flange 2767. Imaging device 2761 can be any suitable camera or detector, which is configured to detect signals emitted by, for example, analytes and / or standards (as described above). For example, imaging device 2761 can be a charge coupled device (CCD) array and / or the like, which can be used to continuously monitor the signals emitted by analytes and / or standards in real time to allow a user to quickly determine whether an analyte is present in a sample, and optionally determine the amount or activity of the analyte. In other embodiments, imaging device 2761 can be a photodiode, for example, the photodiodes 2728 and 2738 described above.

[0158] The seal bracket 2762, one or more seals 2763, the rotating flange 2765, and the transition flange 2767 are collectively configured to couple the imaging device 2760 to the mounting block 2771 of the focusing assembly 2770. In addition, the arrangement of the imaging assembly 2760 isolates the imaging device 2761 from light emitted by external sources (e.g., other than the optical output 2752). In other words, the seal bracket 2762, one or more seals 2763, the rotating flange 2765, and the transition flange 2767 collectively form a light-tight seal between the imaging device 2761 and the mounting block 2771.

[0159] Focusing assembly 2770 includes mounting block 2771, lens holder 2774, lens 2775, mirror holding block 2776, motor 2781, and filter wheel 2784. As described above, mounting block 2771 is coupled to imaging assembly 2760 (e.g., transition flange 2767 or other portion of imaging assembly 2760). Mounting block 2771 is also coupled to mirror holding block 2776 (see, e.g., Fig. 27 ). In other words, the mounting block 2771 is disposed between the imaging assembly 2760 and the mirror holding block 2776. The mounting block 2771 may be of any suitable shape, size, and / or configuration. Fig.28 As shown in FIG. 27 , the mounting block 2771 defines an opening 2772 and a motor recess 2773. The lens holder 2774 receives the lens 2775 and is movably disposed within the opening 2772. The motor 2781 is at least partially disposed within the motor recess 2773 (see, e.g., Fig. 27 ) and is operable to move the lens holder 2774 within the opening 2772 defined by the mounting block 2771. For example, in some embodiments, the motor 2781 can be configured to rotate a pinion gear or the like, which in turn can cause a rack contained in and / or formed by the lens holder 2774 to advance relative to the pinion gear. In this way, the lens holder 2774 can be moved within the mounting block 2771, for example, to focus at least a portion of the light passing through the lens 2775 (e.g., light emitted by the optical output 2752).

[0160] As described above, the mirror holding block 2776 is coupled to the mounting block 2771. The mirror holding block 2776 defines an opening 2778 and includes a mirror adjustment mechanism 2777. More specifically, the mirror adjustment mechanism 2777 is disposed within the opening 2778 defined by the mirror holding block 2776 (see, e.g., Fig. 27). The mirror adjustment mechanism 2777 is configured to receive and / or couple to the mirror 2790 and can be engaged, manipulated, and / or otherwise reconfigured to adjust and / or move the mirror 2790 within the mirror retaining block 2776. The arrangement of the full-column detection portion 2750 is such that the opening 2778 defined by the mirror retaining block 2776 is aligned with, for example, the second optical openings 2415 and 2425 of the first side wall 2411 and the second side wall 2421 of the cartridge holder 2400, respectively. In this way, light emitted from the optical output 2752 can pass through the second optical openings 2415 and 2425 of the cartridge holder 2400 (and the portion of the cartridge 2500 disposed therein) and enter the opening 2778 defined by the mirror retaining block 2776. The mirror 2790 can then be adjusted and / or positioned to direct at least a portion of the light toward the imaging device 2761, as described in further detail herein.

[0161] The filter wheel 2784 is operably coupled to the motor 2781 (e.g., via one or more gears 2782) and is rotatably disposed between the mounting block 2771 and the mirror holding block 2776. The filter wheel 2784 may be of any suitable shape, size, and / or configuration. Fig.28 , the filter wheel 2784 is a relatively thin plate that defines a set of openings 2785. More specifically, in this embodiment, the filter wheel 2784 defines a set of six openings 2785, each of which is configured to receive an optical filter and / or the like (not shown). The optical filter can be any suitable filter, lens, and / or other optical device that is configured to focus, filter, convert, and / or otherwise modify at least a portion of the light passing therethrough. In certain embodiments, each opening 2785 defined by the filter wheel 2784 can include a different filter and / or lens. In this way, the motor 2781 can rotate the filter wheel 2784 to align any one of the filters with the opening 2772 defined by the mounting block 2771. Thus, at least a portion of the light directed toward the imaging device 2761 by the mirror 2790 passes through the desired filter (and lens 2776) before entering the imaging device 2761, as described in further detail herein.

[0162] In some cases, the filter wheel 2784 can be rotated during the electrophoresis run. In this way, alternative imaging modes can be used while the electrophoresis process is occurring. For example, the filter wheel 2784 can be placed in a first position so that the first filter is aligned with the opening 2772 defined by the mounting block 2771, and can then be moved (e.g., rotated) to a second position, a third position, and / or a fourth position to align the second filter, the third filter, and / or the fourth filter with the opening 2772, respectively. In some such cases, for example, the first filter can enable the imaging device 2761 to capture fluorescence induced in a label portion coupled to an analyte: for example, the second filter can enable the imaging device 2761 to capture the natural fluorescence of the first analyte: for example, the third filter can enable the imaging device 2761 to capture the natural fluorescence of the second analyte; for example, the fourth filter can enable the imaging device 2761 to detect the absorbance of the analyte. In other embodiments, the filter wheel 2784 can include any other suitable filter or combination of filters. Alternating images of the entire column (e.g., illuminated by optical output 2752) can be captured at any point during the run by rotating filter wheel 2784. In this way, the fluorescence of the label, the natural fluorescence of the analyte, and / or the absorbance of the analyte can each be tracked individually in a single run as the analyte migrates through the column (e.g., capillary).

[0163] As described above, system 2000, and specifically cartridge holder 2400, can be configured to accept different cartridges, such as molecular weight cartridge 2500' and isoelectric focusing cartridge 2500". Other types of cartridges are also possible, such as isotachophoresis cartridges, capillary electrochromatography, etc. In some cases, cartridge 2500 can be reusable. Similarly stated, cartridge 2500 can be adapted to run an analysis multiple times with the same or different samples.

[0164] like Figures 29 to 37 As shown in FIG. 2 , molecular weight cartridge 2500′ has cartridge body 2501′ and capillary 2530′. Cartridge body 2501′ defines at least one orifice 2505′, at least one vertical registration feature 2510′, and at least one horizontal registration feature 2515′. Fig.18 and Fig.19As described, the vertical alignment feature 2510' can be configured to slidably engage, cooperate with, and / or otherwise interact with the first guide rail 2428 (e.g., upper guide rail) and the second guide rail 2429 (e.g., lower guide rail) of the box holder 2400. More specifically, in this embodiment, the box body 2501' includes a first vertical alignment feature (e.g., upper alignment feature) configured to engage the first guide rail 2428 and a second vertical alignment feature (e.g., lower alignment feature) configured to engage the second guide rail 2429. In some embodiments, the vertical alignment feature 2510' can be, for example, a groove, a notch, a slot, a channel, etc., which is configured to receive a portion of the first guide rail 2428 or the second guide rail 2429 (see, e.g., Fig.29 , Fig.33 and Fig.34 ). Thus, the guide rails 2428 and 2429 and the vertical registration feature 2510' collectively limit and / or substantially prevent the molecular weight box 2500' from moving in the vertical direction.

[0165] The horizontal registration feature 2515' can be similarly configured to cooperate with the latch member 2458 of the cartridge holder 2400. For example, the horizontal registration feature 2515' can be, for example, a notch, groove, slot, channel, etc., which is configured to selectively receive and contact a portion of the latch member 2458 when the latch member 2458 is moved into a locked or locked configuration, such as Fig.33 and Fig.34. The horizontal alignment feature 2515' can have a dog-leg shape so that the latch member 2458 can be rotated into the surface of the box body 2501' defining the horizontal alignment feature 2515' and locked thereon. In this way, the horizontal alignment feature 2515' and the latch member 2458 can jointly prevent the molecular weight box 2500' from moving in the horizontal direction (e.g., in the insertion direction). In addition, when the latch member 2458 engages the horizontal alignment feature 2515', the molecular weight box 2500' can be pulled into the box holder 2400 so that one or more parts of the molecular weight box 2500' are placed in contact with the contact member 2485, as described in further detail herein. In certain embodiments, in response to the surface of the box body 2501' being placed in contact with the sensor 2488, the latch member 2458 can move to contact the horizontal alignment feature 2515'. In certain embodiments, the cartridge body 2501' may also abut against the inner surface of the first side wall 2411 and / or the inner surface of the second side wall 2421 of the cartridge holder 2400 to prevent the molecular weight cartridge 2500' from moving in a horizontal direction (e.g., in a lateral or sideways direction) other than the insertion direction of the cartridge 2500'. In this way, when the latch member 2458 is engaged, the cartridge holder 2400 may limit and / or substantially prevent the molecular weight cartridge 2500' from moving horizontally and / or vertically relative to the cartridge holder 2400.

[0166] The one or more apertures 2505' defined by the cartridge body 2501' may be of any suitable shape, size, or configuration. Figure 29 to Figure 31 As shown in . The molecular weight box 2500' includes a first orifice 2505' arranged on a first side of the box body 2501' and a second orifice 2505' arranged on a second side of the box body 2501', opposite to the first side. More specifically, the first orifice 2505' and the second orifice 2505' are arranged in relative and / or aligned positions. The position of the orifice 2505' is such that when the molecular weight box 2500' is positioned in the box holder 2400, the orifice 2505' is substantially aligned with the central bore 2711 of the central member 2710, for example, contained in the single point detection portion 2701 of the optical assembly 2700. In addition, the capillary 2530' is arranged in the box body 250' so that a portion of the capillary 2530' is aligned with the orifice 2505' and / or between the orifices 2505' (see, e.g. Fig.29 and Fig.30 ), thereby allowing a portion of the capillary 2501 ′ to be visualized through the single point detection portion 2701 of the optical component 2700.

[0167] Capillary 2530' can be configured to be communicated with the sample fluid contained in the sample vial 2367, for example, arranged in the reagent tray 2365. In certain embodiments, the end portion 2532' of capillary 2530' can extend to the outside of the box body 2501' of the molecular weight box 2500'. In other embodiments, capillary 2530' can be communicated with the sample fluid in one or more sample vials 2367 and / or holes 2366 via a pipette tip or other suitable structures protruding from the box body 2501'. In certain embodiments, a sleeve 2535' such as a plastic or carbon sleeve can be arranged around the part of capillary 2530', for example, to increase the rigidity of capillary 2530'. Like this, sleeve 2535' can protect the end portion 2532' of capillary 2530', to prevent its undesirable deformation or rupture. Such sleeve 2535' can, for example, have enough rigidity to pierce the diaphragm or other covering of the sample vial. In certain embodiments, the sleeve 2535' may also provide insulation (eg, thermal and / or electrical insulation) to the end portion 2532' of the capillary tube 2530'.

[0168] The molecular weight box 2500' also includes a pressure line 2550', a pressure port 2551' and a seal 2552', such as Figure 31 to Figure 35 When the molecular weight cartridge 2500' is disposed within the cartridge holder 2400, the pressure line 2550' can be fluidly coupled to the pressure nozzle 2445 via the pressure port 2551' (see, e.g. Fig.35 ). Seal 2552' is configured to be pressed against one or more sample vials 2367 or one or more containers when reagent tray 2365 moves relative to molecular weight box 2500'. For example, reagent tray 2365 can be configured to move in the vertical direction, so that capillary 2530' is placed in fluid communication with sample vial, so that seal 2552' abuts sample vial. System 2000 can be configured to actuate pressure source 2497, which can pressurize sample vial, and push sample from vial into capillary 2530'. Additionally or alternatively, capillary 2530' can be fluidly coupled to vacuum source 2496 via vacuum port 2448 and vacuum interface 2541'. System 2000 can be configured to actuate vacuum source 2496 and / or pressure source 2497 to push sample from vial into capillary 2530'. In some cases, by applying both negative and positive pressure to the sample vial, the volume and / or flow of the sample can be drawn into a capillary '2530' having a desired set of characteristics (eg, having fewer bubbles, turbulence, and / or the like).

[0169] The molecular weight cartridge 2500' also includes a dual septum vial 2540' having an inlet septum 2543' and an outlet septum 2542' (see, e.g. Fig.31 and Fig.35 ). The inlet septum 2543' and / or the outlet septum 2542' can be substantially liquid-impermeable. The inlet septum 2543' is configured to be pierced by the end portion 2531' (opposite to the end portion 2532') of the capillary 2530' to connect the capillary 2530' to the internal volume fluid of the double septum vial 2540' and to communicate electrically. For example, during the current run or during the previous run, the double septum vial 2540' can contain a running buffer that can be delivered to the capillary 2530' and / or can receive and store waste samples from the capillary 2530'. In addition, at least the end portion 2531' of the capillary 2530' is conductive, and therefore, when the end portion 2531' pierces the inlet septum 2543', the end portion 2531' electrically connects or couples the capillary 2530' to the double septum vial 2540'.

[0170] In some embodiments, the outlet septum 2542' can be air-permeable so that when the sample is drawn into the double septum vial 2540' through the capillary 2530', air, but not liquid, can be driven out through the outlet septum 2542'. Additionally or alternatively, the double septum vial 2540' can contain a sponge, a filter, and / or other absorbent material to prevent the sample from leaving the molecular weight box 2500'. In this embodiment, the outlet septum 2542' is pierced by the vacuum interface 2541'. In some cases, after the run is completed, the system 2000 can be configured to dry the double septum vial 2540', for example, by circulating air through the double septum vial 2540'. In some embodiments, the system 2000 can be configured to track and / or determine the amount of sample drawn into the double septum bottle 2540' and warn the user to replace the double septum bottle 2540' and / or the molecular weight box 2500' when the double septum vial 2540' is full and / or after a predetermined number of runs. In some cases, system 2000 may be configured to block at least a portion of operation of system 2000 when dual septum vial 2540' is full.

[0171] When the molecular weight cartridge 2500' is disposed within the cartridge holder 2400', the dual diaphragm vial 2540' is configured to be electrically coupled to at least a portion of the system 2000. For example, when the molecular weight cartridge 2500' is held by the cartridge holder 2400, a portion of the contact member 2485 extending from the first contact bracket 2438 is disposed within the molecular weight cartridge 2500" and in contact with the dual diaphragm vial 2540'. As described above, the contact member 2485 is electrically coupled to a voltage (or current) source, such as the power supply 2210. Thus, the contact member 2485 places the dual diaphragm vial 2540' in electrical contact with the voltage (or current) source. Similarly, the contact member 2485 extending from the second contact bracket 2439 can be placed in contact with a portion of the molecular weight cartridge 2500' and / or a portion of the capillary 2530' to establish an electrical connection therebetween. Thus, the potential can be The electric potential may be applied to the capillary 2530' via the contact bracket 2485 and the double diaphragm vial 2540', which may induce an electromotive force on the analyte within the capillary 2530'. In the case where the analyte is charged, the electric potential may attract the analyte to the end portion 2531' of the capillary 2530' (e.g., toward the double diaphragm vial 2540'). In some cases, the analyte and / or other portions of the sample may flow toward the end portion of the capillary 2530' with a set of characteristics (e.g., mobility parameters, etc.) based at least in part on molecular weight, wherein analytes with smaller molecular weights may travel faster than analytes with larger molecular weights.

[0172] like Figure 35 to Figure 37 As shown in , the molecular weight box 2500' can be arranged in the box holder 2400, and the system 2000 can be set to perform a molecular weight analysis. In some cases, before inserting the molecular weight box 2500', the user can prepare the reagent tray 2365 and / or the molecular weight box 2500'. As described above, the user can then insert the molecular weight box 2500' into the box holder 2400 along a single predetermined orientation. In this way, the molecular weight box 2500' can be placed in the desired position in the box holder 2400 so that the orifice 2505' is aligned with the single point detection optical portion 2701, such as Fig.37 More specifically, the molecular weight box 2500' is positioned within the system 2000 such that the orifice 2505' and, therefore, the capillary 2530' is aligned with the central bore 2711 of the central member 2710. Thus, by aligning the molecular weight box 2500' with the single point detection optical portion 2701, the energy and / or photons emitted by the optical output 2707 can be directed to a predetermined portion of the capillary 2530'.

[0173] Once the molecular weight box 2500' is held in the box holder 2400, the reagent tray 2365 can be moved relative to the molecular weight box 2500' to position at least a portion of the capillary 2530' in the hole of the reagent tray 2365 and / or the sample vial, as described above. In addition, when the molecular weight box 2500' is positioned in the box holder 2400, the capillary 2530' is fluidly coupled to the vacuum source 2496. Therefore, the vacuum source 2496 can then be activated (e.g., at least semi-automatically) to generate a negative pressure differential in the capillary 2530', which is operable to draw the sample into the capillary 2530'. Once the capillary 2530' is disposed within the well and / or sample vial, the contact member 2485 can deliver electrical energy (e.g., current) to the dual diaphragm vial 2540' and portions of the molecular weight box 2500' and / or the capillary 2530' to apply an electrical potential to the sample, which causes the analyte to migrate within the sample. The rate at which the analyte migrates within the capillary 2540' can be related to one or more mobility factors, e.g., molecular weight and / or the like.

[0174] Thus, as the analyte migrates within the capillary 2530', the optical output 2707 can emit energy or photons, which in turn illuminate and / or excite a volume of the sample (the energy or photons are directed) flowing through a predetermined portion of the capillary 2530'. The photodiodes 2728 and 2738 then capture and / or detect at least a portion of the energy and / or photons, which are reflected, refracted and / or absorbed by the analyte, standard, label portion, etc., that is illuminated and / or excited within the volume of the sample. The photodiodes 2728 and 2738 can then send a signal that is associated with and / or includes data about the detection, and the system 2000 (e.g., a processor in the electronic assembly 2200) can analyze the data to determine molecular weight and / or electrophoretic mobility data associated with the analyte in the sample. For example, the length of time between applying the potential and detecting the analyte can be related to the molecular weight and / or mobility factor of the analyte. In other embodiments, the sample flow can be induced by the vacuum source 2496 and / or the pressure source 2497.

[0175] Although the system 2000 is described above as receiving a molecular weight cartridge 2500' and performing molecular weight analysis, in other cases, the system 2000 may receive an isoelectric focusing cartridge 2500" and may be configured to perform electrophoresis and subsequently visualization and detection. Figures 38 to 44As shown in , the isoelectric focusing box 2500" has a box body 2501", a capillary 2530" and a set of electrodes 2560". The box body 2501" defines at least one orifice 2505", at least one vertical alignment feature 2510", and at least one horizontal alignment feature 2515". The one or more vertical alignment features 2510" and the horizontal alignment features 2515" can be similar to those described above with reference to the molecular weight box 2500'. Therefore, the isoelectric focusing box 2500" can be arranged in a similar manner and temporarily secured within the box holder 2400.

[0176] The one or more apertures 2505" defined by the cartridge body 2501" may be of any suitable shape, size, and / or configuration. For example, Figures 38 to 41 As shown in , the orifice 2505" is an elongated opening that is arranged on an opposite side of the box body 2501" (as described above with reference to the molecular weight box 2500'). Therefore, when the isoelectric focusing box 2500" is positioned in the box holder 2400, the orifice 2505" can be optically aligned with the second optical openings 2415 and 2425 of the box holder 2400. In addition, the orifice 2505" can provide optical access to the length of the capillary 2530", so that the full-column detection portion 2750 of the optical assembly 2700 can image the sample before, during and / or after isoelectric focusing. The orifice 2505" and the full-column detection portion 2750 of the optical assembly 2700 can be collectively configured for full-column imaging. Similarly stated, the orifice 2505" can substantially expose the entire length of the capillary 2530" arranged between the electrode sets 2560" (e.g., greater than 90% of the length).

[0177] The isoelectric focusing box 2500" also includes a slit plate 2520". The slit plate 2520" can be optically aligned with the orifice 2505" and / or the capillary 2530". The slit plate 2520" can improve the resolution of the isoelectric focusing image by, for example, reducing the lens effect associated with the curve of the capillary 2530". Similarly stated, the slit plate 2520" can expose the central portion of the capillary 2530" to the full-column detection portion 2750 of the optical assembly 2700 while obstructing the edges of the capillary 2530". In some embodiments, the slit plate 2520" can define a slit width of 100 microns, 200 microns, 300 microns, 500 microns, or any other suitable slit width.

[0178] like Fig.40 and Fig.41As shown in , the isoelectric focusing box 2500" includes a capillary 2530", a pressure line 2550", a pressure port 2551", a seal 2552" and a sleeve 2535", each of which can be structurally and / or functionally similar to the capillary 2530', pressure line 2550', pressure port 2551', seal 2552' and sleeve 2535' described above with reference to the molecular weight box 2500'. Therefore, samples from one or more vials 2367 or wells 2366 of the reagent tray 2365 can be drawn into the capillary 2530" in a manner similar to that described above with reference to the molecular weight box 2500'. The isoelectric focusing box 2500" can be configured to analyze samples with essentially no bulk fluid flow. Therefore, once the sample has been drawn into the capillary 2500", bulk fluid flow can be prevented, as described in further detail herein.

[0179] like Figures 40 to 44 As shown in , the isoelectric focusing box 2500" includes a pinch valve assembly 2570", which includes a vacuum line 2572" and a pinch plate 2571". The pinch valve opening 2520" defined by the box body 2501" is configured to receive the pinch valve actuator 2444 described above with reference to the vacuum portion 2440 of the box holder 2400. The vacuum line 2572" is fluidly connected to the top portion of the capillary 2530". Once the sample is drawn into the capillary 2530", the lever arm 2441 of the box holder 2400 can be rotated so that the pinch valve actuator 2444 applies a force to the vacuum line 2572". The force can cause the vacuum line 2572" to deform against the pinch plate 2571", reducing the cross-section of the vacuum line 2572", thereby closing the pinch valve assembly 2570". When the pinch valve assembly 2570" is closed, the bulk fluid flow within the capillary 2530" can be prevented or impeded. In some cases, the pinch valve assembly 2570" can be closed while a vacuum is applied so that negative pressure is applied to the top portion of the capillary 2530". This negative pressure can offset and / or overcome gravity. Similarly stated, the pinch valve assembly 2570" and / or the negative pressure applied to the capillary 2530" can prevent or impede bulk fluid movement within the vertical column under the action of gravity.

[0180] Although not shown, the isoelectric focusing box 2500" can include a double diaphragm vial similar to the double diaphragm vial 2540' of the molecular weight box 2500' and fluidly connected to the diaphragm 2530". The double diaphragm vial 2540" can contain a running buffer, such as a solution having a higher or low pH. The bottom diaphragm can be configured to allow ion flow between the running buffer and the capillary 2530" while preventing and / or restricting bulk fluid flow. In this way, the double diaphragm vial can induce a pH gradient within the capillary 2530".

[0181] In addition to the double diaphragm vial, the isoelectric focusing box 2500" also includes a waste container 2540". The waste container 2540" can also be fluidly connected to the capillary 2530". Similarly stated, the waste container 2540" can be fluidly parallel to the double diaphragm vial. The waste container 2540" can contain a sponge, a filter, or other suitable material. Once the run has been completed, the pinch valve assembly 2570" can be opened and the sample can be drawn into the waste container 2540" via the vacuum source 2496. For example, the bottom diaphragm of the double diaphragm vial can direct the sample into the waste container 2540", preventing the fluid sample from being drawn out of the box 2500". In some embodiments, the waste container 2540" can function similarly to the waste container 2540' included in the molecular weight box 2500'.

[0182] The isoelectric focusing cartridge 2500" also includes a set of electrodes 2560". In this embodiment, the electrode set 2560" includes two electrodes. The electrodes 2560" can be configured to abut corresponding contact members 2485 (eg, 2486) when the isoelectric focusing cartridge 2500" is disposed within the cartridge holder 2400. Fig.44 ). The contact member 2485 can then be electrically coupled to a voltage (or current) source, such as the power supply 2210 of the electronic assembly 2200. The two electrodes 2560" are also electrically coupled to the capillary 2530" and / or the sample within the capillary 2530". For example, in some embodiments, the capillary 2530" can be conductive, wherein the first end portion 2531" is electrically coupled to the first electrode 2560" and the second end portion 2532" is electrically coupled to the second electrode 2560", such as Fig.44 As shown in . In certain embodiments, an electrode 2560" can be coupled to the above-mentioned double diaphragm vial. In such an embodiment, the double diaphragm vial can be conductive so that the running buffer within the double diaphragm vial can be electrically coupled to the electrode 2560". The system 2000 can be configured to excite the power supply 2210 so as to induce an electric potential along the capillary 2530" containing the sample. The electric potential can cause the analytes within the sample to migrate to their isoelectric points along the pH gradient within the capillary 2530", as described in detail above.

[0183] As described above with reference to the molecular weight cartridge 2500', the user can position the isoelectric focusing cartridge 2500" within the cartridge holder 2400 and can set the system 2000 to, for example, an electrophoresis analysis setting and / or configuration. In some cases, prior to inserting the isoelectric focusing cartridge 2500", the user can prepare the reagent tray 2365 and / or the isoelectric focusing cartridge 2500". As described above, the user can then insert the isoelectric focusing cartridge 2500" into the cartridge holder 2400 along a single predetermined orientation. In this way, the isoelectric focusing cartridge 2500" can be placed in a desired position within the cartridge holder 2400 such that the orifice 2505" is aligned with the full-column detection portion 2750 of the optical assembly 2700, as described above. Fig.42 More specifically, the isoelectric focusing cartridge 2500" is positioned within the system 2000 such that the orifice 2505" and, therefore, the capillary 2530" is aligned with the second optical openings 2415 and 2425 of the cartridge holder 2400, the optical output 2752, and the opening 2778 of the mirror holding block 2776. Thus, by aligning the isoelectric focusing cartridge 2500" with the full column detection 2750, energy and / or photons emitted by the optical output 2752 can be directed to a predetermined portion of the capillary 2530".

[0184] Once the isoelectric focusing cartridge 2500" is retained in the cartridge holder 2400, the reagent tray 2365 can be moved relative to the isoelectric focusing cartridge 2500" to position at least a portion of the capillary 2530" in a well of the reagent tray 2365 and / or a sample vial, as described above. Additionally, when the isoelectric focusing cartridge 2500" is positioned within the cartridge holder 2400, the capillary 2530" is fluidly coupled to the vacuum source 2496. Thus, the vacuum source 2496 can then be activated (e.g., at least semi-automatically) to create a negative pressure differential within the capillary 2530", which is operable to draw a volume of sample into the capillary 2530".

[0185] Once a mixture having desired components (e.g., a sample) is drawn into the capillary 2530", the system 2000 can actuate, for example, the vacuum portion 2440 of the box holder 2400 to insert at least a portion of the pinch valve actuator 2444 into the pinch valve opening 2520" of the box body 2501" and into contact with the pinch valve assembly 2570" of the isoelectric focusing box 2500". In this way, the pinch valve actuator 2444 can place the pinch valve assembly 2570" in a closed configuration by deforming a portion of the vacuum line 2572" against the pinch plate 2571", as described above. Therefore, with the pinch valve assembly 2570" in the closed configuration, a large amount of fluid flow through the capillary 2530" is restricted, constrained and / or substantially prevented. The system 2000 can then apply an electric field to the capillary 2530", for example by delivering an electric current to the contact member 2485. Thus, with the contact member 2485 in contact with the electrode 2560", the electric current similarly excites the electrode 2560" to create a voltage difference between the end portions 2531" and 2532" of the capillary 2530". Thus, in response to the electric current supplied to the capillary 2530", the analytes in the sample migrate and / or separate along the length of the capillary 2530" according to the isoelectric point and / or the like of each analyte, as described in detail above.

[0186] In some cases, the full column detection portion 2750 can detect a "full column" image or signal and / or can otherwise perform a "full column" detection of a sample within the capillary 2530". Similarly stated, the imaging device 2761 can be operable to capture more than a single point along the capillary 2530". For example, the imaging device 2761 can be operable to capture and / or detect a sufficient length to visualize the separation and / or focusing of analytes during electrophoresis processing (e.g., about 1 cm, about 3 cm, about 5 cm, about 10 cm, about 20 cm, about 50 cm, or any other appropriate length of the capillary 2530". Additionally or alternatively, the imaging device 2761 can be operable to capture and / or detect the natural fluorescence and absorbance of the analyte within the capillary 2530". For example, the filter wheel 2784 can be rotated to change the optical signal presented to the imaging device 2761 while the analytes are separated and / or focused within the capillary 2530". Thus, during a single run, the sample can be characterized for native fluorescence, absorbance, and / or any other appropriate optical characteristic along the entire column while the analytes are separated and / or focused.

[0187] In certain embodiments, reagent, reagent tray, capillary box and / or the like can be packaged individually or can be packaged together as a kit for, for example, analyte detection using any one of the systems or methods described herein. In certain embodiments, the kit can include materials for making molecular weight, isoelectric point and / or any other suitable one or more standards (such as those described herein). In addition, one or more migration parts, one or more reactive parts, one or more label parts can be packaged independently or together. In certain embodiments, the kit can include one or more electrophoresis standards, which include peptides, one or more fluorescent dyes and one or more photoreactive groups. In addition, buffer, polymeric or polymerizable materials, blocking solutions and flushing solutions can be packaged together with reagent, reagent tray, capillary box, etc., or can be packaged independently with reagent, reagent tray, capillary box, etc. Components can be provided or mixed separately in dry or liquid form.

[0188] Certain embodiments described herein relate to computer storage products having non-transitory computer-readable media (also referred to as non-transitory processor-readable media) having instructions or computer code thereon for performing various computer-implemented operations. Computer-readable media (or processor-readable media) are non-transitory in the sense that they do not inherently include temporary propagating signals (e.g., propagating electromagnetic waves carrying information on a transmission medium such as space or cables). The media and computer code (also referred to as code) may be those designed and constructed for one or more specific purposes. Examples of non-transitory computer-readable media include, but are not limited to: magnetic storage media, such as hard disks, floppy disks, and magnetic tapes; optical storage media, such as compact disks / digital video disks (CD / DVD), compact disk read-only memories (CD-ROMs), and holographic devices; magneto-optical storage media, such as optical disks; carrier signal processing modules; and hardware devices that are specifically configured to store and execute program code, such as application specific integrated circuits (ASICs), programmable logic devices (PLDs), read-only memories (ROMs), and random access memory (RAM) devices. Other embodiments described herein relate to a computer program product, which may include, for example, the instructions and / or computer code discussed herein.

[0189] Certain embodiments and / or methods described herein may be implemented by software (which is executed on hardware), hardware, or a combination thereof. Hardware modules may include, for example, general purpose processors, field programmable gate arrays (FPGAs), and / or application specific integrated circuits (ASICs). Software modules (which are executed on hardware) may be expressed in various software languages ​​(e.g., computer code), including C, C++, Java, and the like. TM , Ruby, Visual BasicTM And / or other object-oriented, procedural or other programming languages ​​and development tools. Examples of computer code include, but are not limited to, microcode or microinstructions, such as machine instructions generated by a compiler, code for generating network services, and files containing high-level instructions that are executed by a computer using an interpreter. For example, an imperative programming language (e.g., C, FORTRAN, etc.), a functional programming language (Haskell, Erlang, etc.), a logical programming language (e.g., Prolog), an object-oriented programming language (e.g., Java, C++, etc.), or other appropriate programming languages ​​and / or development tools may be used. Additional examples of computer code include, but are not limited to, control signals, encryption codes, and compression codes.

[0190] Although various embodiments have been described above, it will be understood that various embodiments have been present only by way of example and not limitation. Where the schematic diagrams and / or embodiments described above indicate certain components arranged in certain orientations or positions, the arrangement of the components may be modified. Although embodiments have been particularly shown and described, it will be understood that various changes may be made in form and detail. Although various embodiments have been described as having a combination of specific features and / or components, other embodiments may be provided having any feature and / or combination of components from any of the embodiments described above.

[0191] In the case where the above-mentioned method and / or event indicate that some events and / or programs occur in a certain order, the sequencing of some events and / or programs can be modified. Additionally, as required, some events and / or programs can be performed simultaneously and sequentially as described above in parallel processing.

Claims

1. A device for performing capillary electrophoresis, isoelectric point analysis and / or molecular weight analysis of a sample, characterized in that The device comprises: a cartridge holder configured to receive any one of a plurality of capillary cartridges, each of the plurality of capillary cartridges comprising a capillary, wherein the capillary defines an interior volume configured to contain a sample containing an analyte and the capillary is configured for analyte separation; at least one transmitter; and at least one detector, the at least one emitter and the at least one detector being collectively configured to switch between a first configuration in which the at least one detector receives an optical signal from a point on the capillary and a second configuration in which the at least one detector receives a signal associated with at least 1 centimeter of the capillary in length based on which capillary cartridge of the plurality of capillary cartridges is disposed in the cartridge holder.

2. The device according to claim 1, wherein: The plurality of capillary boxes include a molecular weight box and an isoelectric focusing box; the at least one emitter and the at least one detector being collectively configured to operate in a first configuration when the molecular weight cartridge is disposed in the cartridge holder; and The at least one emitter and the at least one detector are collectively configured to operate in a second configuration when the isoelectric focusing cartridge is disposed in the cartridge holder.

3. The device according to claim 1, wherein: The apparatus also includes a reagent tray holder configured to move relative to the cartridge holder to place capillaries of a capillary cartridge of the plurality of capillary cartridges in fluid communication with a reagent.

4. The apparatus according to claim 1, further comprising: A vacuum source is fluidly coupled to the cartridge holder, the cartridge holder being configured to place a portion of a capillary cartridge of the plurality of capillary cartridges in fluid communication with the vacuum source when the capillary cartridge is disposed within the cartridge holder.

5. The device according to claim 1, wherein: The at least one detector comprises a first detector and a second detector, The first detector is a first optical detector configured to detect a first optical output associated with a first sample illuminated by a first light beam emitted from the at least one emitter and substantially converging to a point; The second detector is a second optical detector configured to detect a second optical output associated with a second sample illuminated by a second light beam emitted from the at least one emitter forming the light column.

6. An apparatus for performing capillary electrophoresis, isoelectric point analysis and / or molecular weight analysis of a sample, characterized in that The device comprises: a cartridge holder configured to receive any one of a plurality of capillary cartridges, each of the plurality of capillary cartridges comprising a capillary, wherein the capillary defines an interior volume configured to contain a sample containing an analyte and the capillary is configured for analyte separation; one or more transmitters; and and one or more detectors, the one or more emitters and the one or more detectors being collectively configured to automatically enter a molecular weight imaging mode when a molecular weight cartridge of the plurality of capillary cartridges is disposed in the cartridge holder, and to automatically enter an isoelectric focusing imaging mode when an isoelectric focusing cartridge of the plurality of capillary cartridges is disposed in the cartridge holder.

7. The device according to claim 6, wherein: at least one of the one or more detectors is configured to detect a first optical output associated with a first sample illuminated by a first light beam generated by at least one of the one or more emitters and converging substantially to a point when the one or more detectors and the one or more emitters are in a molecular weight imaging mode; At least one of the one or more detectors is configured to detect a second optical output associated with a second sample when the one or more detectors and the one or more emitters are in an isoelectric focusing imaging mode, and the second sample is illuminated by a second light beam generated by at least one of the one or more emitters to form a light column.

8. The device according to claim 7, wherein: The first light beam is configured to illuminate a point of a first capillary of a molecular weight capillary cartridge of the plurality of capillary cartridges; and The second light beam is configured to illuminate at least 3 centimeters of a second capillary of an isoelectric focusing capillary cartridge of the plurality of capillary cartridges.

9. The device according to claim 7, wherein: The first optical output is at least one of absorbance of the first light beam, fluorescence of a tag moiety induced by the first light beam, or natural fluorescence of an analyte induced by the first light beam.

10. An apparatus for performing capillary electrophoresis, isoelectric point analysis and / or molecular weight analysis of a sample, characterized in that The device comprises: a cassette configured to be oriented such that a longitudinal axis of the cassette is vertical when in use; a capillary tube disposed in the cartridge, the capillary tube being arranged parallel to a longitudinal axis of the cartridge, the capillary tube defining an interior volume configured to contain the sample containing an analyte; and A conductive vial containing a buffer disposed within the cartridge, the conductive vial being configured to be electrically coupled to a first end of the interior volume of the capillary via the buffer.

11. The apparatus according to claim 10, further comprising: a first electrode electrically coupled to the conductive vial; as well as A second electrode is electrically coupled to the capillary between the conductive vial and a second end of the capillary such that the first electrode, the second electrode, and the sample define a portion of an electrical circuit when the interior volume contains the sample.

12. The device according to claim 10, wherein: The buffer is a first buffer, and the apparatus further comprises: a conductive reagent tray holder configured to hold a second buffer; a first electrode electrically coupled to the conductive vial; and A second electrode is electrically coupled to the conductive reagent tray holder such that when the interior volume contains the sample, the first electrode, the second electrode, and the sample define a portion of an electrical circuit.

13. The apparatus according to claim 10, wherein: The conductive vial includes a first septum and a second septum, the buffer being electrically coupled to a first end of the interior volume of the capillary via the first septum.

14. An apparatus for performing capillary electrophoresis, isoelectric point analysis and / or molecular weight analysis of a sample, characterized in that The device comprises: box; a capillary disposed in the cartridge, the capillary defining an interior volume configured to contain the sample containing an analyte, the capillary configured for analyte separation; and a conductive vial containing a buffer disposed within the cartridge, the conductive vial configured to be electrically coupled to a first end of the interior volume of the capillary via the buffer, the conductive vial having a septum configured to be pierced when the cartridge is disposed within a system configured to perform electrophoresis such that the capillary is fluidically coupled to the system via the conductive vial.

15. The apparatus of claim 14, further comprising a tube coupled to an end of the capillary tube such that an analyzer can apply at least one of pressure or vacuum to the capillary tube.

16. The device according to claim 15, wherein: At least a portion of the tube is exposed via an opening in the cassette, the opening being configured to receive a portion of a pinch valve actuator configured to pinch the tube.

17. The device according to claim 16, wherein: The pinch valve actuator is configured to pinch the tube while the analyte migrates within the capillary tube so as to inhibit bulk flow.

18. The apparatus of claim 14, further comprising a bottom membrane configured to allow ion flow between the buffer and the capillary while preventing and / or restricting bulk fluid flow.

19. An apparatus for performing capillary electrophoresis, isoelectric point analysis and / or molecular weight analysis of a sample, characterized in that The device comprises: box; a capillary disposed within the cartridge, the capillary defining an interior volume configured to contain the sample containing an analyte, the capillary configured for analyte separation; a tube disposed within the cartridge body and coupled to an end of the capillary tube such that at least one of pressure or vacuum can be applied to the capillary tube via the tube; and An opening is defined by the cassette through which at least a portion of the tube is exposed, the opening being configured to receive a portion of a pinch valve configured to pinch the tube.

20. The apparatus of claim 19, further comprising a conductive vial containing a buffer and having a first septum and a second septum, the buffer configured to be electrically coupled to the first end of the interior volume of the capillary via the first septum.

21. The apparatus of claim 20, further comprising a bottom membrane configured to allow ion flow between the buffer and the capillary while preventing and / or restricting bulk fluid flow.

22. An apparatus for performing capillary electrophoresis, isoelectric point analysis and / or molecular weight analysis of a sample, characterized in that The device comprises: a cartridge body configured to be disposed within an analyzer; a capillary disposed within the cartridge body, the capillary configured to separate analytes based on isoelectric point; a buffer disposed in a vial within the cartridge body, the buffer configured to induce a pH gradient along the length of the capillary; a first diaphragm disposed between the buffer and the capillary; and A second septum is disposed between the buffer and the analyzer, the second septum being configured to be broken by the analyzer such that at least one of pressure or vacuum can be applied to the vial.

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