Capillary electrophoresis, isoelectric focusing, and molecular weight analysis systems and methods

Abstract

To provide systems that are configured to perform multiple types of analysis, such as electrophoretic mobility and isoelectric electrophoresis within a single device, and that are automated so that multiple samples are analyzed simultaneously or in rapid succession with ease and robustness while consuming minimal volumes of expensive reagents and disposables.SOLUTION: A system includes: a housing; a cartridge retainer disposed within the housing; a detection assembly disposed within the housing; and a reagent tray holder movably disposed within the housing. The detection assembly is configured to transition between a first configuration, in which a first detector detects a first output of at least one emitter, and a second configuration, in which a second detector detects a second output of the at least one emitter. The reagent tray holder is configured to move relative to the cartridge retainer to place the capillary of a capillary cartridge in fluid communication with a reagent volume.SELECTED DRAWING: Figure 6

Description

Technical Field

[0001] Cross - Reference to Related Applications This application claims the benefit of U.S. Provisional Patent Application No. 62 / 278,159, filed on January 13, 2016, the disclosure of which is incorporated herein by reference in its entirety.

[0002] Background Embodiments described herein generally relate to systems and methods for electrophoretically separating and / or analyzing a sample mixture by molecular weight and / or isoelectric point. Some embodiments described herein relate to the separation, detection, identification, classification, and / or quantification of one or more analytes present in a sample. More particularly, embodiments described herein relate to systems and methods configured to perform capillary - based electrophoresis.

Background Art

[0003] Electrophoresis has been used to separate mixtures of molecules based on differences in their migration velocities in an electric field. Generally, electrophoresis refers to the movement of molecules suspended or dissolved in 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. Some known electrophoretic separation modes include separating molecules based at least partially on differences in their mobility in a buffer (generally called zone electrophoresis), separating them based on differences in their mobility in a gel or polymer solution (generally called gel electrophoresis), or separating them based on differences in their mobility in a hydrogen ion concentration (pH) gradient (generally called isoelectric focusing). Because the movement of molecules during electrophoresis can be highly variable, its interpretation is determined by comparison with electrophoretic standards whose behavior and uniqueness have been pre-characterized. Examples of electrophoretic standards include molecular weight (MW) standards in sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and deoxyribonucleic acid (DNA) size standards in agarose gels. In some cases, biomolecule separation can be performed by capillary electrophoresis in a capillary tube. In some cases, the biomolecules (e.g., proteins) can then be visualized by immobilizing them on the wall of the capillary tube. However, consistent capillary electrophoresis and biomolecular visualization can be challenging.

[0004] Biomolecular visualization can be performed using digital imaging. These known analyses utilize imaging devices (e.g., charge-coupled elements, photodiodes, etc.) and lenses or microscopes to acquire images of the sample and / or to detect the sample. In some cases, as the sample flows through the optical system, a light source flashes relatively rapidly to illuminate and / or enable imaging of the flowing biomolecules within a column (e.g., a capillary). The acquired images are then filtered and / or separated to generate images of biomolecular-related features such as labeled fluorescence, intrinsic fluorescence, and / or absorbance. This information can then be compared with known data to characterize and / or identify the biomolecules in the sample.

[0005] While electrophoretic analysis is a method used to determine information related to analytes, proteins, molecules, etc., these methods are typically performed using complex and expensive equipment capable of performing a single analytical mode. Furthermore, some known methods and systems require extensive and / or time-consuming handling and processing steps that negatively impact reproducibility and make automation difficult. [Overview of the Initiative] [Problems that the invention aims to solve]

[0006] Therefore, there is a need for improved systems and methods configured to perform multiple types of analysis, such as electrophoretic mobility and / or isoelectric focusing, within a single device. It is also desirable to automate these techniques to enable the simultaneous, uninterrupted, and easy and robust analysis of multiple samples, while minimizing the consumption of expensive reagents and / or disposable items. [Means for solving the problem]

[0007] overview This specification describes systems and methods for capillary electrophoresis and analytical visualization and characterization. In one embodiment, the system includes a housing, a cartridge retainer disposed within the housing, a detection assembly disposed within the housing, and a reagent tray holder movably disposed within the housing. The cartridge retainer is configured to receive a capillary cartridge having a capillary. The detection assembly includes at least one emitter, a first detector, and a second detector. The detection assembly is configured to transition between a first mode in which the first detector detects a first output of at least one emitter and a second mode in which the second detector detects a second output of at least one emitter. The reagent tray holder is configured to move relative to the cartridge retainer to fluidize the capillary of the capillary cartridge to the reagent volume.

[0008] In another embodiment, the 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 contain a sample containing an analyte. The capillary has a first end defining a first end of the internal volume and a second end defining a second end of the internal volume. The conductive vial contains a buffer solution and has a first partition and a second partition. The buffer solution is electrically coupled to the first end of the internal volume of the capillary via the first partition so that the sample is electrically coupled to the vial when the internal volume contains 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 a portion of the circuit when the internal volume contains the sample. [Brief explanation of the drawing]

[0009] [Figure 1] This is a schematic diagram of a part of a system configured to perform capillary electrophoresis and / or image analytes separated by capillary electrophoresis, according to an embodiment. [Figure 2] This is a perspective view of a system configured to perform capillary electrophoresis and / or image analytes separated by capillary electrophoresis, according to an embodiment. [Figure 3] Figure 2 is a perspective view of the door umbrella included in the housing of the system shown. [Figure 4] Figure 2 is an exploded view of the door assembly included in the housing of the system shown. [Figure 5] This is a front perspective view of a portion of the system shown in Figure 2, with part of the housing missing and the door assembly in Figure 3 shown in the closed position. [Figure 6] This is a front perspective view of a portion of the system shown in Figure 2, with part of the housing missing and the door assembly in Figure 3 shown in the open position. [Figure 7] Figure 2 is a perspective view showing different parts of the system. [Figure 8] Figure 2 is a perspective view showing different parts of the system. [Figure 9] Figure 2 is a perspective view showing different parts of the system. [Figure 10] This is a front perspective view of the reagent assembly and a portion of the housing of the system shown in Figure 3. [Figure 11] This is a rear perspective view of the reagent assembly and a portion of the housing of the system shown in Figure 3. [Figure 12] Figure 10 is an exploded view of the tray portion of the reagent assembly shown. [Figure 13] Figure 2 is a rear perspective view showing a part of the system. [Figure 14] Figure 2 is a front perspective view of the capillary cartridge retainer and optical system assembly included in the system. [Figure 15] Figure 14 is a front perspective view of the capillary cartridge retainer. [Figure 16] Figure 14 is a partially assembled and exploded view of the capillary cartridge retainer. [Figure 17]It is a right rear perspective view of a part of a capillary cartridge retainer shown in FIG. 14. [Figure 18] It is a left front perspective view of a part of a capillary cartridge retainer shown in FIG. 14. [Figure 19] It is a front view of a part of a capillary cartridge retainer shown in FIG. 14. [Figure 20] It is a perspective view of a single point detection part of the capillary cartridge retainer of FIG. 14 and the optical system assembly of FIG. 14. [Figure 21] It is a perspective view of a single point detection part of the optical system assembly shown in FIG. 20. [Figure 22] It is an exploded view of the single point detection part of the optical system assembly shown in FIG. 20. [Figure 23] It is a cross-sectional view of the single point detection part of the optical system assembly along line 23-23 of FIG. 21. [Figure 24] It is a perspective view of the entire column detection part of the cartridge retainer of FIG. 14 and the optical system assembly shown in FIG. 14. [Figure 25] It is a perspective view of the illumination assembly included in the entire column detection part of the optical system assembly shown in FIG. 24. [Figure 26] It is an exploded view of the illumination assembly included in the entire column detection part of the optical system assembly shown in FIG. 24. [Figure 27] It is a perspective view of the camera assembly included in the entire column detection part of the optical system assembly shown in FIG. 24. [Figure 28] It is an exploded view of the camera assembly included in the entire column detection part of the optical system assembly shown in FIG. 24. [Figure 29] It is a left perspective view of a capillary cartridge configured to be used in the system of FIG. 2 during molecular weight analysis. [Figure 30] It is a right perspective view of a capillary cartridge configured to be used in the system of FIG. 2 during molecular weight analysis. [Figure 31] It is a side view of the capillary cartridge of FIG.  29 shown without a part of the cartridge body. [Figure 32] This is a right-side perspective view of the capillary cartridge shown in Figure 29, held within the capillary cartridge retainer shown in Figure 14. [Figure 33] This is a left-side perspective view of the capillary cartridge shown in Figure 29, which is held within the capillary cartridge retainer shown in Figure 14. [Figure 34] This is a left-side perspective view of the capillary cartridge in Figure 29 and the capillary cartridge retainer in Figure 14, shown without side walls. [Figure 35] Figure 31 shows a cross-sectional view of the capillary cartridge and capillary cartridge retainer along line 35-35. [Figure 36] Figure 29 shows the capillary cartridge, Figure 20 shows the single-point detection unit of the optical system assembly, and Figure 14 shows a front perspective view of a portion of the capillary cartridge retainer. [Figure 37] Figure 36 shows a cross-sectional view of the capillary cartridge, the single-point detection unit of the optical system assembly, and the capillary cartridge retainer along line 37-37. [Figure 38] This is a left-side perspective view of a capillary cartridge configured for use in the system shown in Figure 2 during capillary electrophoresis analysis. [Figure 39] This is a right-hand perspective view of a capillary cartridge configured for use in the system shown in Figure 2 during capillary electrophoresis analysis. [Figure 40] Figure 38 is a side view of the capillary cartridge, with part of the cartridge body missing. [Figure 41] Figure 38 is a perspective view of a capillary cartridge, with part of the cartridge body missing. [Figure 42] Figure 38 shows the capillary cartridge, Figure 24 shows the entire column imaging section of the optical system assembly, and Figure 14 shows the cartridge retainer in perspective. [Figure 43] This is a left-side perspective view of the capillary cartridge shown in Figure 38, held within the capillary cartridge retainer shown in Figure 14. [Figure 44] Figure 43 shows a cross-sectional view of the capillary cartridge and capillary cartridge retainer along line 44-44. [Modes for carrying out the invention]

[0010] Detailed explanation This specification describes apparatus, methods, and systems for performing capillary electrophoresis, isoelectric focusing, and / or molecular weight analysis of samples. The apparatus and systems are configured to detect analytes in the sample during and / or after electrophoretic separation.

[0011] In some embodiments, the system includes a housing, a cartridge retainer located within the housing, a detection assembly located within the housing, and a reagent tray holder located movably within the housing. The cartridge retainer is configured to receive a capillary cartridge having a capillary. The detection assembly includes at least one radiator, a first detector, and a second detector. The detection assembly is configured to transition between a first mode in which the first detector detects a first output of at least one radiator and a second mode in which the second detector detects a second output of at least one radiator. The reagent tray holder is configured to move relative to the cartridge retainer to bring the capillary of the capillary cartridge into fluid communication with the reagent volume.

[0012] In some embodiments, the system includes a housing, a cartridge retainer located within the housing, a light source located within the housing, and a detection assembly located within the housing. The cartridge retainer includes a first side and a second side. The first and second sides are substantially parallel and define a space between them configured to receive at least a portion of a capillary cartridge. Each of the first and second sides defines a first and a second aperture. The first and second apertures of the second side are substantially aligned with the first and second apertures of the first side, respectively. The light source is configured to emit a first beam of light and a second beam of light. At least a portion of the first beam of light is directed to pass through the first aperture of the first side and the first aperture of the second side. At least a portion of the second beam of light is directed to pass through the second aperture of the first side and the second aperture of the second side. The detection assembly includes a first detector configured to detect at least a portion of a first beam of light, and a second detector configured to detect at least a portion of a second beam of light.

[0013] In some embodiments, the system includes a housing, a cartridge retainer located within the housing, a detection assembly located within the housing, a reagent tray holder located movably within the housing, a cartridge retainer, and a control assembly located within the housing. The cartridge retainer is configured to receive a capillary cartridge having a capillary. The cartridge retainer includes a plurality of contact surfaces configured to contact the capillary cartridge and to align the capillary cartridge within the cartridge retainer. The detection assembly includes a first emitter and a second emitter, and a first detector and a second detector. The detection assembly is configured to transition between a first and a second form based on one or more properties at least partially related to the capillary cartridge. The first detector is configured to detect the output of the first emitter when the detection assembly is in the first form. The second detector is configured to detect the output of the second emitter when the detection assembly is in the second form. The reagent tray holder is configured to move relative to the cartridge retainer to fluidize the capillary of the capillary cartridge to the reagent volume. The control assembly is configured to receive data related to the capillary cartridge when the capillary cartridge is positioned within the cartridge retainer. Based on the data related to the capillary cartridge, the control assembly is configured to send a signal to the detection assembly to put it into a first or second form.

[0014] In some embodiments, the 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 contain a sample containing an analyte. The capillary has a first end defining a first end of the internal volume and a second end defining a second end of the internal volume. The conductive vial contains a buffer solution and has a first and a second partition. The buffer solution is electrically coupled to the first end of the internal volume of the capillary via the first partition so that the sample is electrically coupled to the vial when the internal volume contains 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 a portion of the circuit when the internal volume contains the sample.

[0015] In some embodiments, the apparatus includes a cartridge body configured to be placed inside an analyzer, a capillary placed inside the cartridge body, and a tube placed inside the cartridge body. The cartridge body defines an opening. The capillary is configured for analyte separation. The tube is coupled to the end of the capillary, thereby allowing the analyzer to apply pressure or vacuum to the capillary. At least a portion of the tube is exposed through 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.

[0016] In some embodiments, the apparatus includes a cartridge body configured to be placed inside an analyzer, a capillary located inside the cartridge body, an outlet tube, an outlet port fluidically coupled to the outlet tube, and a waste container defined inside the cartridge body. The capillary is configured for analyte separation. It is a capillary with an outlet located inside the cartridge body. The outlet tube is coupled to the capillary output. The waste container is fluidically coupled to the outlet tube and configured to prevent liquid from flowing from the outlet tube to the outlet port.

[0017] In some embodiments, the apparatus includes a cartridge body configured to be placed inside an analyzer, a capillary placed inside the cartridge body, a buffer solution placed inside a vial inside the cartridge body, a first partition placed between the buffer solution and the capillary, and a second partition placed between the buffer solution and the analyzer. The capillary is configured to separate the analyte based on its isoelectric point. The buffer solution is configured to create a pH gradient along the length of the capillary. The second partition is configured to be broken by the analyzer so that at least one of pressure or vacuum can be applied to the vial.

[0018] As used herein, the singular forms "a," "an," and "the" refer to multiple objects unless otherwise explicitly indicated. For example, the term "member" is intended to mean a single member or combination of members, and "material" is intended to mean one or more materials or combinations thereof.

[0019] As used herein, the terms “about” and “approximately” generally mean plus or minus 10% of the stated value. For example, about 0.5 includes 0.45 and 0.55, about 10 includes 9 to 11, and about 1000 includes 900 to 1100.

[0020] As used herein, the term “set” can refer to multiple features or a single feature having multiple parts. For example, when referring to a set of walls, the set of walls can be considered as a single wall having multiple parts, or as multiple separate walls. Thus, elements composed of a single structure can include sets of walls. Such sets of walls can include multiple parts that are either continuous or discontinuous with respect to each other. Sets of walls can also be manufactured from multiple elements that are made separately and then joined together (e.g., by welding, adhesive or any preferred method).

[0021] As used herein, the terms “perpendicular” and / or “right-angled” generally describe a relationship between two geometric structures (e.g., two lines, two planes, a line and a plane, etc.) in which those two geometric structures are positioned at substantially 90°. For example, if one line and another line intersect at an angle substantially equal to 90°, then one line is said to be “perpendicular” to the other line. Similarly, if the surfaces of a plane (e.g., a two-dimensional plane) are said to be “perpendicular” to the surfaces of another plane, then those surfaces are positioned at substantially 90° (e.g., substantially orthogonal) as they extend infinitely.

[0022] As used herein, the term “module” refers to any assembly and / or set of operationally coupled electrical components, which may include, for example, memory, processors, electrical traces, optical connectors, software (executed in hardware), etc. 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 in the processor) that can perform one or more predetermined functions related to the module.

[0023] As used herein, the terms “analyte” and / or “target analyte” refer to any molecule or compound separated and / or detected by the methods, apparatus and systems provided herein. Suitable analytes include, but are not limited to, small chemical molecules such as environmental molecules, clinical molecules, chemicals, pollutants and / or biomolecules. More specifically, such chemical molecules include, but are not limited to, insecticides, insecticides, poisons, therapeutic and / or abuse drugs, antibiotics, organic materials, hormones, antibodies, antibody fragments, antibody molecular complexes (e.g., antibody-drug complexes), 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, cofactors, nucleotides, polynucleotides (including ribonucleic acid and / or deoxyribonucleic acid), transition state analogs, inhibitors, receptors, receptor ligands (e.g., nerve receptors 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 biomolecules and / or non-biomolecules, along with fragments and combinations thereof. In some embodiments, the analyte is a protein or protein complex, and the sample is a cell lysate or purified protein. Other suitable analytes include aggregates, clumps, flocs, and / or dispersed phase droplets or particles of colloid and / or emulsion.

[0024] As used herein, the term “sample” refers to a composition containing one or more analytes to be detected. In some embodiments, a sample may be heterogeneous and contain various components (e.g., various proteins) or homogeneous and contain one component (e.g., a population of one protein). Depending on the circumstances, the sample may be a natural biological material and / or a synthetic material. Furthermore, the sample may be in an undenatured form (e.g., a cell suspension) or a denatured form (e.g., a lysate). Depending on the circumstances, the sample may be a single cell (or, for example, a cell lysate from a single cell, or a single cell content as a purified protein) or a multi-cell (or, for example, a cell lysate from a multi-cell, or a multi-cell content as a purified protein from a multi-cell), a blood sample, a tissue sample, a skin sample, a urine sample, a water sample, and / or a soil sample. Depending on the circumstances, the sample may be of biological origin such as eukaryotes, prokaryotes, mammals, humans, yeast, and / or bacteria, or the sample may be of viral origin.

[0025] In some embodiments, the sample is a heterogeneous biological sample or derived from a heterogeneous biological sample, such as a tissue lysate, cell lysate, or a mixture of biomolecules such as proteins (e.g., purified proteins). In further embodiments, the protein in the cell lysate is the analyte to be detected by the methods and systems described herein. In further embodiments, the apparatus, systems and methods provided herein enable the detection of specific forms of proteins, such as phosphorylated proteins. The cell lysate may be, for example, a lysate of a single cell or a mixture of cells. Furthermore, the cell lysate may be single-cell type or multiple-cell type. In some embodiments, the cell type may include stem cells or cancer cells, or a population of stem cells or a population of cancer cells. In one embodiment, the sample includes one or more stem cells (e.g., any cells capable of infinitely differentiating and producing specialized cells). Preferred examples of stem cells include, but are not limited to, embryonic stem cells (e.g., human embryonic stem cells (hES)) and non-embryonic stem cells (e.g., mesenchymal cells, hematopoietic cells, induced pluripotent stem cells (iPS cells), or adult stem cells (MSCs)).

[0026] Depending on the circumstances, the sample may be treated before detecting the analyte in the sample using the apparatus and systems provided herein. For example, the sample may be subjected to dissolution, denaturation, heating, purification (e.g., protein purification), precipitation, immunoprecipitation, column chromatography, centrifugation, etc. In some embodiments, the sample is subjected to a denaturation step before detecting and / or separating the target analyte in the sample using the methods, apparatus and systems described herein. In some embodiments, the treatment step on the sample is performed in one of the apparatus or systems described herein. In other embodiments, the treatment step is performed before introducing the sample into one of the apparatus or systems shown herein.

[0027] As used herein, the terms “standard” and / or “internal standard” refer to a substance with known characteristics (e.g., known isoelectric point, known molecular weight, electrophoretic mobility profile, number of base pairs in the case of nucleic acids, molecular composition, etc.) that can be added to a sample containing an analyte for comparative purposes. In some embodiments, a known amount of standard is added to a sample containing one or more analytes, and both the standard and the molecules in the sample containing the analytes are separated based on their isoelectric points by electrophoresis. Subsequently, a quantitative or semi-quantitative measurement of the amount of analyte originally present in the sample is obtained by comparing the signals of the standard with those of the analytes.

[0028] Generally, isoelectric focusing (IEF) standards are known based on their established isoelectric points. Similarly, molecular weight standards are known. In some cases, standards and / or analytes can be detected by one or more detection molecules or reagents, such as by an antibody against the analyte or by a labeled portion attached to the standard. In some embodiments, a primary antibody is used to bind to the target analyte, and a secondary antibody conjugated to a fluorescent or chemiluminescent reagent is introduced to bind to the primary antibody or primary antibody-analyte complex. The signal of the fluorescent or chemiluminescent molecule is then detected. In other cases, standards and / or analytes can be detected via intrinsic fluorescence (e.g., via the fluorescence of tryptophan amino acids in the standard and / or analyte) and / or absorbance.

[0029] Subsequently, the concentration of the analyte in the sample can be measured by comparing the signal of the standard substance with the signal of the analyte. Furthermore, or by alternative methods, the relative properties of the analyte (e.g., isoelectric point, molecular weight, etc.) can be determined by comparison with the standard substance.

[0030] In some embodiments, the internal standard may be a purified form of the analyte itself, which is generally distinguishable from the analyte in some way. Optional methods for obtaining a purified form of the analyte include, but are not limited to, purification from natural sources or purification from laboratory-cultured organisms (e.g., by chemical synthesis). Distinctive characteristics of the internal standard may include, but are not limited to, any preferred modifications, such as dye labeling, radiometric labeling, or modification of the mobility of the standard during electrophoretic separation so that the standard is distinguishable from the analyte. For example, the analyte and the internal standard may be labeled with fluorescent dyes detectable at discrete emission wavelengths, respectively, thereby making the analyte and standard individually detectable. In some cases, the internal standard may be different from the analyte but behave similarly or in the same way as the analyte, enabling relevant comparative measurements. In some embodiments, suitable reference materials for use may be any of those described in U.S. Patent Application Publication No. 2007 / 0062813, “Electrophoresis Standards, Methods and Kits,” filed September 20, 2006, the disclosure of which is incorporated herein by reference in whole.

[0031] In some cases, the apparatus, systems, and methods provided herein allow for the detection and characterization of multiple analytes from a single sample in a single capillary tube. For example, in some embodiments, the multiple analytes are a population or subpopulation of proteins. In this regard, it may not be practical to include one internal standard corresponding to each individual protein in the protein population or subpopulation. Therefore, in some embodiments, a general isoelectric point standard is introduced into the systems and apparatus provided herein. In some embodiments, the standard is a ladder standard that can operate to exhibit different isoelectric points along the capillary tube. Proteins in the sample moving during electrophoresis are compared to the ladder to determine the isoelectric points of the proteins present in the sample. In some embodiments, multiple ladder standards are used.

[0032] The analytes and / or standards described above are separated in some embodiments by any preferred mobility parameter, such as charge, molecular weight, or electrophoretic mobility (e.g., influenced by molecular weight, characteristic length, area or volume, oligonucleotide length, or other preferred properties). For example, in some embodiments, the sample is subjected to electrophoretic separation in a capillary tube containing a separation matrix based on mobility parameters such as isoelectric point. The capillary tube may contain a separation matrix that can be automatically added. In some embodiments, the separation matrix is ​​an isoelectric separation matrix and has properties similar to or substantially the same as polymer gels used in conventional electrophoretic experiments, such as pH gradients. Capillary electrophoresis in the separation matrix is ​​similar to separation in polymer gels such as polyacrylamide gels or agarose gels, where molecules are separated based on their mobility parameters in the sample by providing porous channels through which molecules can move.

[0033] In some embodiments, once separation is complete, the separated components of the sample (including, for example, the analyte and / or standard substance) can be immobilized on the capillary wall using any suitable method, including, but not limited to, chemical, photochemical, and thermal treatments. In some embodiments, the separated components of the sample are immobilized in a fluid channel (defined, for example, by a capillary) after the molecules have been separated by electrophoresis. For example, in some embodiments, immobilization occurs by exposing the separated sample and capillary to ultraviolet (UV) light, which plays a role in immobilizing the analyte (if present in the sample) and molecules in the sample on the capillary wall. Immobilization can be by covalent or non-covalent means, such as by hydrophobic or ionic interactions. In another embodiment, a reactive portion can be used to covalently immobilize one or more of the decomposed analytes in the fluid channel. The reactive portion can be attached directly or indirectly to the fluid channel (for example, to the wall of the capillary tube). In some embodiments, the reactive portion can be supplied in solution or suspension and, upon activation, may be configured to form crosslinks between the fluid channel walls and molecules in the sample. The reactive portion can cover the inside of the fluid channel or may be present on the linear or crosslinked polymer of the fluid channel, either before and / or after activation, or may not bond to the fluid channel walls. The reactive portion may be and / or include any reactive group capable of forming covalent bonds with the corresponding reactive group of individual molecules in the sample, such as those described above.

[0034] In some embodiments, the reactive moiety includes functional groups that can be converted into functionalities that adhere to the analyte through hydrophobic interactions, ionic interactions, hydrogen bonding, etc. In some embodiments, these reactive moieties can be activated with ultraviolet light, laser, temperature, or any other energy source to immobilize the analyte on the surface of the fluid channel and / or on the surface of particles adhering to the surface of the fluid channel. In some embodiments, the surface of the fluid channel is functionalized with a thermoresponsive polymer that allows for a change in surface hydrophobicity as the temperature changes. In some embodiments, the analyte is immobilized on such a surface by increasing the hydrophobicity of the thermoresponsive polymer when the fluid channel reaches a specific temperature. In yet another embodiment, the analyte can be probed and / or detected without first being immobilized on the surface of the fluid channel. As an example, the analytes can be separated based on their isoelectric points (e.g., by isoelectric focusing electrophoresis) and maintained at their respective isoelectric points, at least as long as an electric current is applied to the sample in the fluid channel. In other words, once the analytes and / or standard materials are separated, the apparatus and / or systems described herein can continue to provide a current that is operable to maintain (e.g., immobilize) the analytes and / or standard materials at their respective isoelectric points.

[0035] The immobilized and / or otherwise separated analytes and / or standard substances are then probed and detected by one or more detection reagents. The detection reagents may bind to or interact with the analytes and / or standard substances to be detected. The detection reagents may enable detection of the standard substances and analytes by any means, including but not limited to fluorescent dyes, optical dyes, chemiluminescent reagents, radioactivity, particles, magnetic particles, paramagnetic particles, etc. The detection reagents may include any organic or inorganic molecules, such as proteins, peptides, antibodies, enzyme substrates, transition state analogs, cofactors, nucleotides, polynucleotides, aptamers, lectins, small molecules, ligands, inhibitors, drugs and other biomolecules, as well as non-biomolecules that can bind to the analytes to be detected. In some embodiments, the detection reagent includes one or more labeled moieties (as described above). In some embodiments, the detection reagent includes one or more labeled moieties. In embodiments using two or more labeled moieties, each labeled moiety may be the same, or some or all of the labeled moieties may be different.

[0036] In some embodiments, the detection reagent is used as a secondary reagent. For example, in some embodiments, the detection reagent is designed to bind a first molecule or a complex of the first molecule to the analyte and / or standard substance, which is then introduced to bind to the analyte and / or standard substance. For example, in some embodiments, a “primary” monoclonal or polyclonal antibody is first introduced into a capillary tube containing the immobilized sample. This “primary” antibody binds to the analyte of interest (if present in the sample), and the unbound primary antibody is flushed away. Next, a “secondary” antibody is introduced, which is designed to bind to either the primary antibody or the region where the primary antibody-analyte complex is spread. The secondary antibody includes a labeling portion for detecting and / or visualizing the presence or absence of the analyte of interest.

[0037] In some embodiments, multiplex immunoassays are performed in the apparatus and systems provided herein to detect the presence or absence of two or more target analytes (e.g., two, three, four, or five analytes) in a sample, or to quantify the amounts of two or more analytes in a sample. In further embodiments, the detection reagent is the same for each of the target analytes. For example, the detection reagent for each analyte is a secondary antibody conjugated to a chemiluminescent label, such as horseradish peroxidase. Differentiation between analytes is achieved by first introducing a specific primary antibody into a capillary tube, where each primary antibody is uniquely specific to a target analyte.

[0038] The labeled portion bound to the secondary antibody can be any suitable label. For example, general labels can include optical dyes (e.g., coloring or fluorescent dyes); chemiluminescent labels, phosphorescent labels, enzymatic labels (e.g., alkaline phosphatase and / or horseradish peroxidase), bioluminescent labels, isotopic labels (e.g., radioactive or heavy isotopes), mass labels and / or particle labels (e.g., colloids, magnetic particles, etc.). In some embodiments, the labeled portion is a chemiluminescent portion. In further embodiments, the chemiluminescent portion is horseradish peroxidase (HRP). In some embodiments, HRP is bound to the secondary antibody and used in immunoassays to detect one or more analytes in a sample. In some embodiments, the labeled portion can be a single isomer dye. In some embodiments, the labeled portion can be a fluorescent dye that can contain any entity that gives a fluorescent signal. For example, the fluorescent dye may include a resonance-delocalized system or an aromatic ring system that absorbs light at a first wavelength and fluoresces at a second wavelength in response to the absorption event. The fluorescent dye may be any of the various classes of fluorescent compounds, such as xanthenes, rhodamines, fluoresceins, cyanines, phthalocyanines, squaline, bolus dyes, coumarins, oxazines, and carvopyronines. In some embodiments, the fluorescent dye is 5-carboxytetramethylrhodamine (5-TAMRA) and / or any other preferred class of fluorescent compound.

[0039] In some embodiments, the labeling portion may be and / or include a chemiluminescent label. A preferred labeling portion may include an enzyme that can react with a chemiluminescent substrate so as to induce chemiluminescent photon emission. For example, an enzyme may induce chemiluminescence of other molecules by its enzymatic activity. Such enzymes may be and / or include peroxidases, e.g., horseradish peroxidase (HRP), β-galactosidase, phosphatase, etc. In some embodiments, the chemiluminescent label can be selected from any of various classes of luminol labels, isoluminol labels, etc. In some embodiments, the detection reagent may include a chemiluminescent substrate such as a Galacton substrate available from Applied Biosystems in Foster City, California, or a SuperSignal West Femto Maximum Sensitivity substrate available from Pierce Biotechnology, Inc. in Rockford, Illinois, or any other suitable substrate. In some embodiments, the detection reagent may be any of those described in U.S. Patents 6,689,576, 6,395,503, 6,087,188, 6,287,767, 6,165,800 and 6,126,870, the disclosures of which are incorporated herein by reference in their entirety.

[0040] In some embodiments, the labeled portion may be and / or contain a bioluminescent compound (for example, found in biological systems where catalytic proteins increase the efficiency of chemiluminescent reactions). 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.

[0041] In some embodiments, the labeling portion may be and / or contain a fluorescent dye. Such fluorescent dyes may include a resonance delocalization system or an aromatic ring system that absorbs light at a first wavelength and fluoresces at a second wavelength depending on the absorption event. The fluorescent dye may be any of various classes of fluorescent compounds, including, but are not limited to, xanthenes, rhodamine, fluorescein, cyanine, phthalocyanine, squaline, bodypi dyes, coumarin, oxazine, and carvopyronine. In some embodiments, for example, if the detection reagent contains a phosphor such as a fluorescent dye, the fluorescence of the phosphor is detected by exciting the phosphor with a suitable light source and monitoring the fluorescence of the phosphor with a detector highly sensitive to the characteristic fluorescence emission wavelength of the phosphor.

[0042] As described above, in some embodiments, two or more different agents can be used to bind to or interact with two or more different analytes, enabling the simultaneous detection of two or more types of analytes. In some embodiments, two or more different detection reagents can be detected simultaneously, each binding to or interacting with one analyte. In various embodiments, by using two or more different detection reagents, one agent, for example, a primary antibody, can bind to or interact with one or more analytes to form a first agent-analyte complex, and a second reagent, detection reagent, for example, a secondary antibody, can be used to bind to or interact with the first agent-analyte complex.

[0043] In another embodiment, two different detection reagents, for example, antibodies for both phosphorylated and non-phosphorylated forms of the analyte, may enable the detection of both forms of the analyte. In some embodiments, one predetermined detection reagent, for example, an antibody, may enable the detection and analysis of both phosphorylated and non-phosphorylated forms of the analyte. In some embodiments, multiple detection reagents can be used with multiple substrates to enable color multiplexing. For example, different chemiluminescent substrates can be used to emit photons of different colors. Selective detection of different colors (e.g., by diffraction gratings, prisms, a series of color filters, etc.) may enable the determination of which color of photon is being emitted at any given position along the fluid path (e.g., along a molecular weight gradient), and therefore which detection reagent is present at each emission position. In some embodiments, different chemiluminescent reagents can be supplied sequentially, enabling the sequential detection of different bound detection reagents.

[0044] In general, during standard immunoassay processes performed in the apparatus and systems described herein, some of the internal standards are lost due to various washing processes. Therefore, it is generally desirable to load a sufficient amount of internal standards into the sample at the start of the assay so that the internal standards remaining in the capillary after the immunoassay can generate a sufficient signal, allowing for curve calibration and adjustment to analyze the molecular weight and / or uniqueness of the analyte (e.g., number of amino acids or oligonucleotide base pairs). However, a relatively large amount of internal standards can interfere with analyte capture if the standard and analyte are in the same position. Therefore, some standards may not be located with the analyte during and / or at the end of electrophoresis. However, such standards may not produce a reliable calibration curve for analyte detection. Therefore, in some embodiments, the sample may contain two or more standards. For example, an internal standard may be formed by and / or contain a first standard (called a "bright standard" or "positioning standard") and a second standard (called a "dim standard"). The bright standard may be a standard with properties different from those of the analyte (e.g., isoelectric point). Therefore, after electrophoresis, the positions of the positioning standard and the analyte will be far apart from each other within the capillary. Consequently, the fluorescence emitted from the bright standard and the analyte will not overlap or interfere with each other. The dim standard may be a standard with properties similar to those of the analyte (e.g., isoelectric point). Therefore, after electrophoresis, the positions of the positioning standard and the analyte will be close together within the capillary.

[0045] High-luminosity standards can be positioned along a channel (defined, for example, by a capillary tube) at a location different from the analyte, providing coordinates (e.g., anchor points) for low-luminosity standards to be positioned near or at the same location as the analyte, thereby providing an accurate calibration curve. Generally, after the internal standard and analyte are separated, the high-luminosity standard produces fluorescence that is brighter than that emitted by the low-luminosity standard. The difference in luminosity between the high-luminosity and low-luminosity standards may be due to differences in emission properties and / or differences in the amounts of the two standards contained in the internal standard. For example, a large amount of high-luminosity standard and a small amount of low-luminosity standard can be mixed to form a standard that can produce a "high-luminosity" signal from the high-luminosity standard and a "low-luminosity" signal from the low-luminosity standard. Thus, after the electrophoretic separation step, a "high-luminosity" signal from the high-luminosity standard and a "low-luminosity" signal from the low-luminosity standard are detected. In some embodiments, the internal standard material may include high-brightness and low-brightness standard materials, such as those described in U.S. Patent Application Publication 2011 / 0011740, the disclosure of which is incorporated herein by reference in whole.

[0046] The embodiments described herein facilitate one or more analyses of one or more analytes (e.g., by molecular weight analysis and / or isoelectric focusing) in a single system, and subsequent visualization and detection of the analytes in the sample. The embodiments described herein can provide the functions of a pipette and a microfluidic path, thereby enabling the analysis of very small sample volumes. Such apparatus and / or systems may include any suitable devices, mechanisms, assemblies, subassemblies, electronic devices, actuators, etc., which may enable the apparatus and / or system to separate, immobilize and / or detect, for example, any suitable target analytes. More specifically, the apparatus and systems described herein are configured to accept a cartridge containing one or more capillaries and to expose at least a portion of the cartridge to a negative differential pressure (e.g., generated by a vacuum source) that can operate to draw a certain amount of fluid (e.g., one or more reagents, samples, buffers, washes, detectors, analytes, amphoteric electrolytes, etc.) from one or more wells or trays contained in the apparatus and / or system into the capillaries of the cartridge.

[0047] In some embodiments, such cartridges may have at least one capillary fixed to and coupled to the cartridge body. The capillary (referred to hereafter in the singular for simplicity) is configured to be in fluid communication with one or more fluid reservoirs (e.g., located within the cartridge body and / or located within or defined by the reagent tray). In some embodiments, one or more fluid reservoirs may be wells, etc., containing a fluid containing a component having any of the chemical properties described above. In some embodiments, at least a portion of the cartridge may be conductive (e.g., formed from copper, platinum, stainless steel, conductive microplate plastic, carbon-injected plastic, conductive polymer, and / or any other suitable material). In some embodiments, such a portion of the cartridge may have a volume resistivity of less than 25 ohmcm (Ω·cm) and a surface resistivity of 1000 ohms (or 1 kiloohm (kΩ)) to 100 kΩ. In other embodiments, the cartridge and / or a portion thereof is substantially non-conductive.

[0048] The cartridge capillary defines a lumen that receives at least a portion of the sample, solution, reagent, analyte, and / or any other suitable fluid or gel. The capillary can be of any suitable shape, size, or configuration and can be formed from any suitable material (e.g., glass, plastic, silicon, fused silica, gel, PYREX® (amorphous glass), etc.) that allows liquids and / or dissolved molecules to flow through the lumen. For example, in some embodiments, the length of the capillary is determined at least in part based on factors such as the size or amount of the sample and the magnitude of sample separation when decomposing the analyte or target analyte (e.g., about 2 cm to about 20 cm), in which case a longer capillary can increase sample separation, thereby facilitating the decomposition of complex mixtures and / or mixtures with low abundances of analytes. In some embodiments, the cartridge capillary can be an elongated member having a 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 may be based at least in part on the sample, the amount of the sample, and / or the type of analyte (e.g., having an inner diameter of about 10 micrometers or "microns" (μm) to about 1000 μm). For example, a capillary with a relatively small inner diameter may be associated with a relatively small amount of sample, which may be suitable for expensive samples or reagents, and / or can be used for other purposes. Conversely, a capillary defining a relatively large inner diameter may be associated with a relatively large amount of sample, and / or can be used for other purposes, which may, in some cases, result in improved signal detection, etc. In other embodiments, the inner diameter may be based at least in part on the analysis being performed (e.g., molecular weight-based separation, isoelectric focusing, etc.).

[0049] Figure 1 is a schematic diagram of part of a system 1000 configured to perform capillary electrophoresis (for example, based on molecular weight and / or isoelectric point) according to an embodiment. For example, the user may load a capillary cartridge into system 1000 and provide commands to system 1000 to initiate and / or otherwise cause the system to separate analytes (e.g., proteins) in a sample by molecular weight at least semi-automatically. In such cases, system 1000 captures digital or analog images related to the detection of analytes in a sample (e.g., any suitable drug, reagent, protein, analyte, buffer, lysate, etc.) drawn into the capillary of the capillary cartridge. Thus, system 1000 can analyze the images and / or other data related to the detection and provide molecular weight and / or morphological data of the components of the sample. In other cases, the user may load a capillary cartridge into system 1000 and provide commands to system 1000 to initiate and / or otherwise cause the system to separate analytes in a sample by isoelectric point at least semi-automatically. In such cases, system 1000 draws the sample (e.g., any suitable drug, reagent, protein, analyte, buffer, lysate, etc.) into the capillary, separates and / or focuses the analytes in the sample within the capillary, detects the presence or absence of the target analyte, and / or detects the position of the analytes in the sample (e.g., analytes that have moved to different positions along the capillary related to their isoelectric point). Optionally, system 1000 can immobilize at least some components of the sample within the capillary (e.g., by heat, UV exposure, etc.) before detecting the target analyte.

[0050] As shown in Figure 1, the system 1000 includes a housing 1100, a reagent tray assembly 1300, a capillary cartridge retainer 1400, and a detection assembly 1700. Although not shown in Figure 1, in some embodiments the system 1000 may include any suitable electronic system or assembly (e.g., a hardware module and / or a software module stored in memory and executed in the processor) having at least a power supply, a processor, and memory, which can be configured and / or otherwise programmed to perform one or more processes related to performing at least semi-automated electrophoretic separation. Similarly, the system 1000 may include any suitable fluid channel system or assembly defining one or more fluid channels configured to receive fluids that can flow through the system 1000, such as a sample, one or more reagents, air, etc., as will be described in further detail herein with respect to specific embodiments.

[0051] As described above, system 1000 is configured to receive a capillary cartridge 1500 (also referred to herein as the “cartridge”). The cartridge 1500 may include at least one body 1510 fixedly coupled to at least one capillary 1530. The cartridge 1500 may be any preferred shape, size, or configuration. In some embodiments, the cartridge 1500 may be configured to be associated with a particular analysis and / or used in other particular analyses. For example, in some cases, system 1000 may receive a cartridge configured for use in molecular weight analysis. In other cases, system 1000 may receive a cartridge configured for use in an isoelectric focusing process. In some embodiments, the cartridge 1500 may have a size, shape, and / or configuration that makes the cartridge suitable for any of the analyses. Furthermore, the cartridge 1500 may include any preferred identification tag, code, and / or device that can be automatically detected by system 1000 when the user places the cartridge 1500 into system 1000.

[0052] The housing 1100 of system 1000 can be any preferred shape, size, or configuration and can be arranged to at least partially enclose or at least partially house any preferred component of system 1000. For example, the housing 1100 can at least partially enclose the reagent tray assembly 1300, the capillary cartridge retainer 1400, and the detection assembly 1700. Although not shown in Figure 1, in some embodiments, the housing 1100 can be configured to form one or more parts, chambers, internal volumes, etc., which are configured to allow at least some of the components of system 1000 to be placed inside. In some embodiments, the housing 1100 may include a door, which is configured to allow access to the internal volume defined by the door. For example, a user can open the door of the housing 1100 to place a capillary cartridge 1500 inside the capillary cartridge retainer 1400, as described in further detail herein. In some embodiments, at least a portion of the housing 1100 may be opaque, thereby preventing a substantial amount of light from leaking through the housing into the chamber defined by the housing. In some embodiments, the housing 1100 can define at least one conditioned 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., illuminance).

[0053] The capillary cartridge retainer 1400 (also referred to herein as the "cartridge retainer") is fixedly positioned within the housing 1100. For example, in some embodiments, the cartridge retainer 1400 can be coupled to a frame or the like that maintains the cartridge retainer 1400 in a substantially fixed position within the housing 1100. In some embodiments, as described in further detail herein, the cartridge retainer 1400 may also be coupled to and / or otherwise positioned in a fixed position relative to the detection assembly 1700.

[0054] The cartridge retainer 1400 may be any preferred shape, size, or configuration. For example, the cartridge retainer 1400 may include a set of side walls defining an internal volume configured to receive at least a portion of a capillary cartridge 1500 (also referred to herein as the “cartridge”). More specifically, the cartridge retainer 1400 may have or define a substantially C-shaped cross-section, with at least one face of the cartridge retainer 1400 being substantially open. Thus, the user can insert the cartridge 1500 through the substantially open face of the cartridge retainer 1400 to position at least a portion of the cartridge 1500 within the internal volume. In some embodiments, the cartridge retainer 1400 may include a latch mechanism suitable for forming a friction fit, snap fit, screw connection, etc., with at least a portion of the cartridge 1500 to connect the cartridge 1500 to the cartridge retainer 1400. In other words, the cartridge retainer 1400 holds the cartridge 1500 in a substantially fixed position relative to the cartridge retainer 1400 by at least temporarily connecting to the cartridge 1500 when a portion of the cartridge 1500 is inserted into its internal volume.

[0055] The cartridge retainer 1400 is configured to receive the cartridge 1500 in a predetermined orientation (e.g., only one orientation or direction). Although not shown in Figure 1, the cartridge retainer 1400 may include any preferred alignment features or sensors configured to engage with and / or detect a portion of the cartridge 1500 when the cartridge 1500 is placed within the cartridge retainer 1400. More specifically, the cartridge retainer 1400 may include, for example, any number of features (e.g., protrusions, openings, grooves, etc.), assemblies, mechanisms, sensors, etc., each of which engages with and / or detects a portion of the cartridge 1500 to ensure that the cartridge 1500 is held in a desired position and / or orientation within the cartridge retainer 1400.

[0056] In some embodiments, the cartridge retainer 1400 may include and / or be coupled to any suitable assembly, mechanism, device, etc. configured to engage with the cartridge 1500 to control the flow of fluid through at least a portion of the cartridge 1500. For example, in some embodiments, the cartridge retainer 1400 may include and / or be coupled to a vacuum source or assembly configured to generate negative pressure within the volume of the cartridge 1500, such as the lumen of a capillary. The vacuum source may be fluidly coupled to a portion of the cartridge retainer 1400 via a port, etc., that fluidly connects the vacuum source to the cartridge when the cartridge 1500 is held by the cartridge retainer 1400. Optionally, the vacuum source may be activated (for example, by a manual switch and / or by an electrical switch included in an electrical circuit and controlled by a processor) to generate negative pressure within the cartridge 1500, as will be described in detail with respect to specific embodiments. In some embodiments, the cartridge retainer 1400 may include a device or mechanism configured to engage with the cartridge 1500 to selectively restrict the bulk flow of fluid through a portion of the cartridge 1500. For example, the cartridge retainer 1400 may include an actuator that selectively contacts a pinch valve or the like contained in the cartridge 1500 to restrict and / or substantially block the bulk flow of fluid through the lumen of the capillary contained in the capillary cartridge 1500.

[0057] The cartridge retainer 1400 may also include any number of electrical contacts, etc., configured to electrically couple a portion of the cartridge 1500 to an electrical or electronic assembly included in the system 1000. For example, in some embodiments, the cartridge retainer 1400 includes one or more conductive contact members, clips, surfaces, etc., which contact the relevant conductive contact members, clips, surfaces, etc., of the cartridge 1500 when the cartridge 1500 is held inside it. In some embodiments, at least a portion of the cartridge 1500 can be formed from a conductive material such as stainless steel or conductive plastic. Thus, when the cartridge 1500 is held in a desired position within the cartridge retainer 1400, one or more conductive members, etc., of the cartridge retainer 1400 contact one or more predetermined conductive portions of the cartridge 1500, thereby enabling the cartridge 1500 to communicate electrically or electronically with the electrical and / or electronic assembly included in the system 1000. As an example, as will be described in more detail herein, the cartridge retainer 1400 can electrically connect the conductive capillary of the cartridge 1500 and / or the conductive fluid within the lumen of the capillary to the electrical assembly and / or electronic assembly of the system 1000.

[0058] The reagent tray assembly 1300 of system 1000 may be of any preferred shape, size, or configuration and may be arranged to receive, contain, and / or store at least a portion of reagent trays (not shown in Figure 1). The reagent tray assembly 1300 may receive and / or include any preferred reagent trays (not shown in Figure 1). For example, a reagent tray may hold and / or otherwise define sets of wells, well plates, microwell plates, troughs, etc. Wells and / or microwells may be of any preferred size and may be arranged along and / or defined by such surfaces of the reagent tray in any preferred arrangement. While specific examples of reagent trays are described herein, the reagent tray assembly 1300 may be configured to receive and / or include any preferred reagent tray of similar size and / or shape that can define any number and / or arrangement of wells and / or microwells. Wells and / or microwells contained in or defined by the reagent tray can hold any suitable amount of solution, fluid, gel, lysate, buffer, sample, analyte, amphoteric electrolyte, drug, reagent, protein, substrate, etc. In some embodiments, the wells and / or microwells can hold vials, etc., containing a certain amount of any suitable fluid. In some embodiments, the reagent tray assembly 1300 and / or a portion of the reagent tray assembly 1300 is conductive and electrically coupled to the electrical assembly and / or electronic assembly included in the system 1000. In such embodiments, the reagent tray and / or a portion of the reagent tray may also be conductive, and coupling the reagent tray to the reagent tray assembly 1300 facilitates electrical connection to the fluid placed in the reagent tray.

[0059] At least a portion of the reagent tray assembly 1300 is movably positioned within the housing 1100 and / or movably coupled to the housing 1100. For example, the reagent tray assembly 1300 can be movably coupled to one or more tracks, racks, lead screws, slides, pistons, etc., which may be operable to move the reagent tray assembly 1300 relative to the housing 1100. As indicated by arrow AA in Figure 1, the reagent tray assembly 1300 (or at least the reagent tray contained therein) can be moved toward or away from the cartridge retainer 1400. In other words, when the cartridge 1500 is held by the cartridge retainer 1400, the reagent tray assembly 1300 can be moved in a direction parallel to the axis defined by the capillary 1530 of the cartridge 1500. Furthermore, as indicated by arrow BB, the reagent tray assembly 1300 can be moved in one or more directions along a plane perpendicular to the cartridge retainer 1400. In other words, when the cartridge 1500 is held by the cartridge retainer 1400, the reagent tray assembly 1300 (or the reagent tray contained therein) can be moved along a plane perpendicular to the axis defined by the capillary 1530 of the cartridge 1500. In other words, within the housing 1100, the reagent tray assembly 1300 (or at least the reagent tray contained therein) can be moved in the X direction (e.g., left or right), the Y direction (e.g., up or down), and the Z direction (e.g., forward or backward) relative to the cartridge retainer 1400.

[0060] Thus, the reagent tray assembly 1300 is configured to move at least the reagent tray (not shown in Figure 1) relative to the cartridge 1500 held by the cartridge retainer 1400 in order to position at least one end of one or more capillaries 1530 of the cartridge 1500 into the wells, microwells, vials, etc. of the reagent tray. Furthermore, the reagent tray assembly 1300 can move at least the reagent tray through any number of suitable positions relative to the cartridge 1500 and / or the cartridge retainer 1400 in order to position one or more capillaries 1530 into any of the wells, microwells, and / or vials contained in the reagent tray, or any suitable combination thereof. Therefore, a negative pressure can be generated within the capillary 1530 when the capillary 1530 is in fluid communication with a vacuum source (as described above), and the negative pressure can act to draw some amount of fluid, such as described above, from any suitable one or more wells of the reagent tray into the capillary 1530. Furthermore, or alternatively, the wells, microwells, vials, etc. can be fluidically coupled to a positive pressure source via pressure conduits (not shown in Figure 1) inserted into the wells, microwells, vials, etc. together with the capillary 1530. Parts of the reagent tray assembly 1300, the capillary 1530, and / or cartridge 1500 may be operable to seal the wells, microwells, vials, etc. to the cartridge 1500 so that positive pressure can push fluid from the wells, microwells, vials, etc. into the capillary 1530.

[0061] The detection assembly 1700 of system 1000 is fixedly positioned within the housing 1100. As described above, the detection assembly 1700 is also positioned in a predetermined and fixed position relative to the cartridge retainer 1400. For example, the detection assembly 1700 can be positioned within the housing 1100 such that a predetermined portion of the detection assembly 1700 is aligned with a predetermined portion of the cartridge retainer 1400 and / or otherwise positioned in a desired position relative to it. In some embodiments, the detection assembly 1700 and / or the cartridge retainer 1400 may include any suitable adjustment mechanism, etc., to ensure the desired alignment between the detection assembly 1700 and the cartridge retainer 1400.

[0062] The detection assembly 1700 may be any suitable device, mechanism and / or assembly configured to take in and / or detect digital or analog data (e.g., images) of the analyte and / or standard material, and / or detect signals emitted by the analyte and / or standard material. For example, in some embodiments, the detection assembly 1700 includes a first radiator 1705, a second radiator 1751, a first detector 1728, and a second detector 1760. The first radiator 1705 of the detection assembly 1700 may be any suitable device, component, mechanism, assembly, etc. configured to emit energy (e.g., heat, photons, radiation, etc.). For example, in some embodiments, the first radiator 1705 may be one or more LEDs, deuterium lamps, lasers, incandescent light sources, fluorescence sources, or any other suitable light sources. In some embodiments, the first radiator 1705 can be optically coupled to the cartridge retainer 1400, cartridge 1500, and / or capillary 1530 via one or more lenses, mirrors, prisms, optical fibers, etc. For example, the first radiator 1705 can be powered and / or excited to emit photons having a predetermined wavelength and / or wavelength range. In some embodiments, the detection assembly 1700 may include one or more mirrors, lenses, filters, etc. configured to direct, focus, and / or convert the wavelength of photons emitted by the first radiator 1705. For example, the detection assembly 1700 may include any suitable lens and / or filter (e.g., a TAMRA filter) related to chemiluminescence, fluorescence (e.g., intrinsic fluorescence, fluorescence of a labeled portion, etc.), absorbance, etc.

[0063] Similarly, the second emitter 1751 can be any suitable device, component, mechanism, assembly, etc. configured to emit 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 respect to the first emitter 1705. In some embodiments, the first emitter 1705 is configured to emit photons, for example, during molecular weight analysis, and the second emitter 1751 is configured to emit photons, for example, during isoelectric focusing electrophoresis. In such embodiments, the first emitter 1705 can be, for example, a single optical fiber output (e.g., a single focused beam of light), while the second emitter 1751 can be, for example, an optical fiber output, a grid array of LEDs, etc. (e.g., a row of light rather than a single focused beam of light). In other embodiments, a single emitter can be used during molecular weight analysis and isoelectric focusing electrophoresis (e.g., via one or more apertures, filters, barriers, reflectors and / or refractors, etc.). In yet another embodiment, the detection assembly 1700 may include more than the first radiator 1705 and the second radiator 1751. As described in further detail herein, the first radiator 1705 (or more radiators) and the second radiator 1751 (or more radiators) may 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 retainer 1400.

[0064] The first detector 1728 and the second detector 1760 may be any suitable digital or analog detector. For example, in some embodiments, the first detector 1728 and / or the second detector 1760 may be and / or include a photodiode, an array of photodiodes, a charge-coupled device (CCD) array, etc. The detectors 1728 and 1760 can be used to capture images and / or signals related to the analyte and / or standard material in the sample. In some embodiments, the detectors 1728 and 1760 may be operable to periodically and / or continuously capture images and / or signals emitted from the analyte and / or standard material. In some embodiments, the detectors 1728 and 1760 may be operable to monitor the analyte and / or standard material in real time or substantially in real time, thereby enabling the user to quickly determine whether the analyte is present in the sample, the amount or activity of the analyte, the molecular weight of the analyte, etc. In some embodiments, for example, during molecular weight analysis, the first detector 1728 can be used to detect and / or image the flow of sample through the capillary 1530 of cartridge 1500 (configured in this case for use in molecular weight analysis) in substantially real time while cartridge 1500 is held by cartridge retainer 1400. In some embodiments, a 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 as the analytes separate and focus, and / or after the analytes have been focused and optionally immobilized. Similarly, the second detector 1760 detects signals (e.g., fluorescence, absorbance, etc.) associated with one or more analytes contained in the sample separated in the capillary 1530 of cartridge 1500 (configured in this case for use in isoelectric focusing) while cartridge 1500 is held by cartridge retainer 1400.Furthermore, the detection assembly 1700 can be operably coupled to any suitable electrical or electronic circuit and configured to transmit signals to and / or receive signals from a processor, etc. (for example, the detection assembly 1700 can transmit one or more signals to a processor, etc. so that data related to the captured image and / or detected signals is stored, for example, in memory or a database). The detection assembly 1700 is described as including a first detector 1728 and a second detector 1760, but in other embodiments, the detection assembly 1700 may include a single detector or a number of (e.g., three or more) detectors configured to detect a portion of the energy (e.g., photons) generated by the radiators 1705 and / or 1751.

[0065] For example, the system 1000 can be configured and programmed to perform molecular weight analysis of a sample, which may include, for example, preparing the sample and / or reagents, along with preparing the cartridge 1500, when in use. The user can then insert the cartridge 1500 into the cartridge retainer 1400 in a single predetermined orientation, as described above. The cartridge retainer 1400 then binds to the cartridge 1500, at least temporarily, to hold the cartridge 1500 in a substantially fixed position. The arrangement of the cartridge retainer 1400 and the detection assembly 1700 within the housing 1100 is such that predetermined parts of the detection assembly 1700 (e.g., the first emitter 1705 and the first detector 1728) are aligned with predetermined parts of the cartridge retainer 1400 (e.g., the first set of openings). Therefore, by aligning the detection assembly 1700 with the cartridge retainer 1400, and with the cartridge retainer 1400 holding the cartridge 1500 in a predetermined fixed position, for example, a portion of the capillary 1530 of the cartridge 1500 can be aligned with the first radiator 1705 and the first detector 1728. Thus, the energy and / or photons emitted by the first radiator 1705 can be directed to a predetermined portion of the capillary 1530.

[0066] As described above, the cartridge 1500 (including, for example, the capillary 1530) is fluidly coupled to the vacuum source when it is placed in the cartridge retainer 1400. Thus, the vacuum source can then be operated (e.g., at least semi-automatically) to generate a negative differential pressure that can be operated to draw a substantially continuous flow of sample through the capillary 1530. With the sample flowing through the capillary 1530 in this manner, the first radiator 1705 can emit energy or photons, thereby illuminating and / or activating a certain amount of sample flowing through a predetermined portion of the capillary 1530 (to which 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 related to the illuminated and / or activated analyte, standard material, etc. in that amount of sample. Furthermore, or by alternative means, the first detector 1728 can acquire and / or detect one or more images, image data and / or signals related to light absorbed by an analyte, standard substance, etc. The images and / or data can then be analyzed to obtain molecular weight-based data, electrophoretic mobility, size-based data and / or morphological data related to the analyte in the sample.

[0067] Similarly, the system 1000 can be configured and programmed, and / or otherwise configured, to detect signals from one or more analytes contained in a sample separated and / or focused within the capillary 1530 of cartridge 1500 (configured in this case for use in isoelectric focusing) while capillary electrophoresis is being performed and / or cartridge 1500 is held by cartridge retainer 1400. In such cases, the user can insert cartridge 1500 (configured in this case for use in isoelectric focusing) into cartridge retainer 1400 in a single predetermined orientation, as described above. Therefore, by aligning the detection assembly 1700 with the cartridge retainer 1400 (for example, thereby aligning the second radiator 1751 and the second detector 1760 with, for example, a second set of apertures), and with the cartridge retainer 1400 holding the cartridge 1500 in a predetermined fixed position, the second radiator 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 radiator 1751 can emit energy or photons directed towards a predetermined portion of the capillary 1530 (for example, a predetermined length of the capillary 1530 or a corresponding column).

[0068] Depending on the circumstances, the second radiator 1751 and the second detector 1760 can collectively acquire a “whole column” image of the sample in the capillary 1530 and / or perform “whole column” detection. Similarly, the second radiator 1751 and the second detector 1760 may be operable to acquire and / or detect more than a single point along the capillary 1530. For example, the second radiator 1751 and the second detector 1760 may be operable to acquire a length sufficient to visualize the separation and / or focus of the analyte during the electrophoresis process. The second radiator 1751, the second detector 1760 and optionally additional optical components may be operable to define optical paths of approximately 1 cm, 3 cm, 5 cm, 10 cm, 20 cm, 50 cm, or any other suitable length along the capillary 1350. Furthermore, or alternatively, the second emitter 1751 and the second detector 1760 may be operable to capture the intrinsic fluorescence, labeled fluorescence, and / or absorbance of the analyte, standard material, etc., in the capillary 1530. For example, while the analyte is separated and / or focused in the capillary 1530, a filter wheel (not shown in Figure 1) may be operable to modify the optical signal presented to the second detector 1760. Thus, while the analyte is separated and / or focused during a single run, the sample can be characterized along the entire column for intrinsic fluorescence, labeled fluorescence, absorbance, and / or any other suitable optical properties.

[0069] As described above, depending on the negative differential pressure generated by the vacuum source, a certain amount of mixture (e.g., one or more reagents, samples, buffers, washes, detectors, analytes, amphoteric electrolytes, antibodies, labels, etc.) can be drawn into the capillary 1530. However, if the system 1000 is configured to perform isoelectric focusing, once a desired amount of sample or other desired fluid is drawn into the capillary 1530, the cartridge retainer 1400 and / or any other suitable part of the system 1000 may engage with a part of the cartridge 1500 to move, for example, a pinch valve, to a closed position, thereby restricting and / or substantially blocking the bulk flow of fluid through the capillary 1530. Furthermore, the system 1000 can apply an electric field to the conductive parts of the cartridge 1500 (e.g., the fluid in the capillary 1530 and / or the capillary 1530, as described above). Therefore, an electric current can flow along the capillary 1530, and the analytes in the mixture are separated by an 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 immobilize the molecules in the capillaries of cartridge 1500. For example, a second radiator 1751 can emit energy or photons (e.g., a column of light or fluorescence) directed at a predetermined portion of the capillary 1530 (e.g., a predetermined length of the capillary 1530 or a corresponding column), thereby illuminating, activating, and immobilizing that amount of separated sample or mixture in the corresponding column of the capillary 1530.

[0070] With the sample components (e.g., including one or more analytes) separated, the separated analytes and / or standard substances contained in the sample are probed with one or more reagents, which may include any suitable drugs, reagents, antibodies specific to the analyte, HRP-conjugated secondary antibodies, or any combination thereof, as described in detail above. Subsequently, a signal is generated from one or more labeled moieties (e.g., isotope-labeled, immunolabeled, optical dyes, enzymes, particles, or combinations of particles such as chemiluminescent-labeled antibodies or fluorescently labeled antibodies) using the detection reagent, and this signal is taken up or detected by the second detector 1760. In other embodiments, the intrinsic fluorescence and / or absorbance characteristics of the analyte can generate a signal to be taken up by the second detector 1760. For example, the analyte (e.g., a protein, a part of a protein such as tryptophan amino acids, etc.) can be excited with the second emitter 1751 and detected by the second detector 1760. In other cases, the second detector 1760 can detect the reduction of light emitted from the characteristic second emitter 1751 of the analyte absorbance peak. Thus, molecular weight analysis and / or isoelectric focusing can be performed at least semi-automatically using system 1000.

[0071] Although described above as immobilizing molecules in the sample, in other embodiments, the system 1000 does not need to immobilize molecules in the sample. For example, after the sample is separated and / or focused, the first detector 1728 and / or the second detector 1760 can capture a final image of the capillary 1530 and / or detect molecules in the sample before the sample is flushed into a waste container and / or the sample is recaptured or otherwise discarded. In such embodiments, the cartridge 1500 may be reusable so that subsequent samples can be separated and / or focused using the same cartridge 1500 and / or capillary 1530.

[0072] Figures 2 to 44 show a system 2000 configured to perform capillary electrophoresis, such as molecular weight measurement and / or isoelectric focusing measurement, according to embodiments. System 2000 includes a housing 2100 and / or support structure (Figures 2 to 8), an electronics assembly 2200 (Figure 8), a reagent assembly 2300 (Figures 9 to 13), a cartridge retainer 2400 (Figures 14 to 20), and an optical system assembly 2700 (Figures 20 to 28). System 2000 is configured to receive cartridges such as a molecular weight cartridge 2500' (Figures 29 to 37) and / or an isoelectric focusing cartridge 2500'' (Figures 38 to 44). As will be described in more detail herein, system 2000 can at least semi-automatically characterize analytes in a sample by molecular weight and / or isoelectric focusing. System 200 may be capable of drawing a sample (including, for example, any suitable drug, reagent, protein, analyte, buffer, lysate and / or any other substance described herein) into one or more capillaries of cartridge 2500' and / or 2500'' (generally referred to herein as “cartridge 2500''” (see, for example, Figure 7)) and imaging a certain amount of sample flowing through it. Furthermore, System 2000 may be capable of separating the sample at least semi-automatically (by capillary electrophoresis) and imaging the sample during and / or after separation, for example by whole-column detection.

[0073] As shown in Figures 2 to 8, the housing 2100 and / or support structure (hereinafter referred to as the “housing”) may be of any preferred shape, size, and / or configuration and may be positioned to at least partially enclose or at least partially support any preferred component 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. As shown in Figure 2, the cover 2110 is coupled to the base 2112 to collectively cover, house, and / or surround at least a portion of the system 2000.

[0074] The door 2130 of the housing 2100 is coupled to a portion of the cover 2110 and / or frame 2120 and can move between a closed and open configuration relative to the cover 2110 to isolate or allow access to portions of the system 2000 located within the cover 2110. As shown in Figures 3 and 4, 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 to the door 2130. The hinge 2132 is coupled 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 that is rotatably coupled to a second portion. Thus, the first and / or second parts may be configured to rotate and / or pivot about an axis (not shown) to transition the door 2130 between a closed position (e.g., Figure 5) and an open position (e.g., Figure 6).

[0075] The door cover 2133 is positioned around the door frame 2131. In some embodiments, the door cover 2133 may be transparent and configured to limit the amount of light entering the internal volume defined by the cover 2110. In other embodiments, the door cover 2133 may include an observation window, etc., configured to allow a user to visualize a portion of the system 2000 located within the cover 2110. The handle 2133 of the door 2110 is operatively coupled to a latch 2135, which can be operated by a user to transition the latch 2135 between a first mode (e.g., latched or locked mode) and a second mode (e.g., unlocked or unlatched mode). The latch 2135 is configured to selectively engage with the door retaining assembly 2140 to selectively prevent movement of the door 2130 relative to the cover 2110. As further described herein, the sensor 2136 is configured to detect and / or sense the relative position of the door 2130.

[0076] For example, as shown in Figures 6 and 7, 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 with the latch 2135 of the door 2130 to selectively hold the latch 2135 in a fixed position (e.g., to at least temporarily hold the door 2130 in a closed position). The actuator 2142 may be any suitable actuator configured to cause the release mechanism 2141 to transition between a first mode in which the release mechanism 2141 engages with the latch 2135 and a second mode in which the release mechanism 2141 disengages from the latch 2135. For example, in some embodiments, the actuator 2142 may be an electromechanical actuator configured to mechanically move a portion of the release mechanism 2141 in response to a signal or command received, for example, from an electronics assembly 2200 or other control device.

[0077] The door retaining assembly 2140 further includes one or more proximity sensors 2143 configured to detect the relative position of the door 2130. For example, in some embodiments, one or more proximity sensors 2143 can be configured to detect the proximity of 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 sensors 2143 of the door retaining assembly 2140 can collectively detect and / or determine, for example, the position and / or configuration of the door 2130 relative to the cover 2110 and / or other parts of the housing 2100. Furthermore, the sensors 2136 and / or 2143 can be configured, for example, to transmit signals related to the position and / or configuration of the door 2130 to the electronic equipment assembly 2200 and / or other control devices, thereby activating parts of the system 2100 (for example, when the door 2130 is in the closed position) and / or preventing parts of the system 2100 from activating (for example, when the door 2130 is in the open position).

[0078] The frame 2120 is configured to support one or more portions of the system 2100. For example, the frame 2120 includes at least an optical support member 2121 configured to support at least a portion of the optical assembly 2700, and an electronic assembly support member 2122 configured to support the electronic assembly 2200 and / or at least a portion of the optical assembly 2700. The theater cover 2114 is coupled to the frame 2120 and configured to at least partially isolate a portion of the system 2100 (see, for example, Figures 6 and 7). In some embodiments, the theater cover 2114 may be a shield configured to block, limit, and / or substantially prevent unwanted exposure of a portion of the system 2000 to light (e.g., from outside the cover 2110).

[0079] The electronics assembly 2200 may be in any preferred configuration and may include any preferred components that enable the electronics assembly 2200 to control the system 2000 at least partially. For example, as shown in Figure 8, the electronics assembly 2200 includes at least a power supply 2210, a printed circuit board assembly (PCBA) 2212, and one or more fans 2215 configured to cool the components of the electronics assembly 2200. As will be described in more detail herein, the PCBA 2212 telecommunicates with one or more system components, such as a pump, light, camera, detector, motor, sensor, auxiliary PCBA, and / or other preferred devices. Not shown in Figure 8, the power supply 2210 may be electrically connected to an external electrical circuit to receive a flow of current from the power grid (e.g., "plugged in"). The power supply 2210 can then regulate, transform, and / or convert the flow of current before it is sent to the electronic PCBA 2212 (e.g., converted from alternating current (AC) to direct current (DC)). Furthermore, the power supply 2210 can be configured to supply current to one or more pumps, motors, actuators, lights, detectors, cameras, sensors, etc., as described in more detail herein.

[0080] PCBA2212 may include any suitable electronic devices or components. For example, PCBA2212 includes at least memory and a processor (not shown). The memory may be, for example, random access memory (RAM), a memory buffer, a hard drive, read-only memory (ROM), erasable programmable read-only memory (EPROM), etc. In some embodiments, the memory may store instructions for causing the processor to execute modules, processes and / or functions related to the control of at least some of the system 2000. The processor may be any suitable processing device capable of running and / or executing sets of instructions or code. 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), etc. The processor may run and / or execute sets of instructions or code stored in memory related to the control of at least some of the system 2000. For example, the processor may execute sets of instructions or code stored in memory related to the control of one or more pumps, motors, actuators, sensors, lights, cameras, etc. Furthermore, as will be described in more detail herein, the processor may execute a set of instructions or codes stored in memory relating to sending a current flow to a portion of the cartridge assembly 2500 to initiate and / or perform electrophoresis.

[0081] As shown in Figures 9 to 13, the reagent assembly 2300 of system 2000 includes at least a drive unit 2310 and a tray unit 2340. The drive unit 2310 is configured to move the tray unit 2340 of the reagent assembly 2300 in response to one or more signals received, for example, from an electronics assembly 2200. As shown in Figures 10 and 11, the drive unit 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 unit 2310 further includes a first slide track 2313, a second slide track 2317, and a third slide track 2322. The first motor 2311 is fixedly coupled to the base plate 2113, which is further 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.

[0082] Although not shown in Figures 9 to 13, the first slide track 2313 is configured to slidably receive the slide block. For example, in some embodiments, the first slide track 2313 may include one or more grooves, channels, slots, tracks, etc., configured to receive and / or slidably engage with a portion of the slide block (not shown). The slide block is then coupled to the slide plate 2318. In other embodiments, the slide block and slide plate 2318 are formed as a single unit or integrally. Furthermore, the slide plate 2318 is coupled to the end of the first drive screw 2312. For example, in some embodiments, the slide plate 2318 may include a mounting plate or bracket and / or be coupled thereto (e.g., via one or more mechanical connectors, welds, adhesives, etc.), and the mounting plate or bracket further forms a screw connection with the first drive screw 2312. Therefore, as will be described in more detail herein, when the first motor 2311 is actuated, the output of the first motor 2311 rotates the first drive screw 2312 relative to the mounting plate or bracket of the slide plate 2318, and thus moves the slide plate 2318 in a linear direction along the length of the first slide track 2312 (for example, towards or away from the first motor 2311).

[0083] The second motor 2315 and the second slide track 2317 of the drive unit 2310 are each coupled to the slide plate 2318. More specifically, the second slide track 2317 is coupled to and / or otherwise included in the slide plate 2318 and extends along the length of the slide plate 2318 in a direction perpendicular to the first slide track 2313. As described above with respect to the first slide track 2313, the second slide track 2317 is configured to slidably receive a slide block (not shown), the slide block is further coupled to a slide bracket 2323. The slide bracket 2323 is further coupled to the end of the second drive screw 2316. Therefore, as will be described in more detail herein, when the second motor 2315 is actuated, the output of the second motor 2315 rotates the second drive screw 2316 relative to the slide bracket 2323, and thus moves the slide bracket 2323 in a linear direction along the length of the second slide track 2316 (for example, towards or away from the second motor 2315).

[0084] The third slide track 2322 is coupled to the slide bracket 2323, as shown in Figures 10 and 12, and is configured to extend along the length of the slide block 2323 in a direction perpendicular to each of the first slide track 2313 and the second slide track 2316. As described above with respect to the first slide track 2313 and the second slide track 2316, the third slide track 2322 is configured to slidably receive the slide block 2342 (Figure 12), and the slide block 2342 is further coupled to the mounting plate 2344 of the tray section 2340. The third motor 2320 is coupled to the motor mount 2345 of the mounting plate 2344, such that the end of the third drive screw 2321 extends through the motor mount 2345 and is rotatably coupled to the slide bracket 2323. As shown in Figures 10 and 11, the third drive screw 2321 extends in a direction substantially parallel to the third slide track 2322 (for example, perpendicular to the base plate 2113 and / or 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 rotates the third drive screw 2321 relative to the third motor 2320, and thus the third motor 2320 moves along the length of the third drive screw 2321. Thus, 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 slide block 2342) to move linearly along the length of the third slide track 2322 (for example, towards or away from the slide plate 2318).

[0085] The arrangement of the drive unit 2310 allows the drive unit 2310 to move the tray portion 2340 of the reagent assembly 2300 in any preferred direction along a plane parallel to the base plate 2113 and perpendicular or perpendicular to that plane, in response to one or more signals from the electronic assembly 2200. In other words, the drive unit 2310 can move the tray portion 2340 in the X, Y, and Z directions. Furthermore, by coupling the second motor 2315 to a slide plate 2318 movably coupled to the first slide track 2313, and the third motor 2320 to a mounting plate 2344 movably coupled (at least indirectly) to the second slide track 2316 and the third slide track 2322, the drive unit 2310 can be configured to simultaneously operate the first motor 2311, the second motor 2315, and the third motor 2322 to move the tray portion 2340 in any preferred direction in the XY plane, the XZ plane, and / or the YZ plane. As shown in Figures 10 and 11, the drive unit 2310 also includes a cable track 2325 that can receive one or more wires and / or conduits. Thus, one or more wires and / or conduits can move (for example, within and / or simultaneously with the cable track 2325) relative to the slide plate 2318 and slide bracket 2323 in response to the operation of the first motor 2311, the second motor 2315 and / or the third motor 2320.

[0086] The tray section 2340 of the reagent assembly 2300 may be of any preferred shape, size, and / or configuration. As shown in Figure 12, the tray section 2340 includes a mounting plate 2344, a condenser 2350, a cold block 2360, a tray holder 2362, a reagent tray 2365, and a shroud 2368. Each of the condenser 2350, cold block 2360, reagent tray 2365, and shroud 2368 is coupled to the tray holder 2362, which is further coupled to the mounting plate 2344 and / or otherwise supported by the mounting plate 2344. Thus, with the mounting plate 2334 coupled to the slide block 2342 (as described above), the mounting plate 2344 and the slide block 2342 slidably couple the tray section 2340 of the reagent assembly 2300 to the drive unit 2310 of the reagent assembly 2300. In some embodiments, the drive unit 2310 can position the tray unit 2310 in a default or other predetermined position when the system 2000 is not in use and / or before or after moving the tray unit 2310. In some embodiments, the shroud 2368 can be coupled to the tray holder 2362 such that at least a portion of the shroud 2368 is substantially aligned with the corresponding portion of the theater cover 2114 (see, for example, Figure 6). In this way, the shroud 2368 and the theater cover 2114 can collectively isolate a portion of the system 2000 within the housing 2100.

[0087] The reagent tray 2365 is configured to be at least temporarily attached to the tray holder 2362. For example, the reagent tray 2365 may be removably attached to the tray holder 2362, thereby allowing the user to remove and / or replace the reagent tray 2365 (for example, for cleaning). As described in further detail herein, the reagent tray 2365 may be attached to the tray holder 2362 such that its surface is in contact with the surface of the cold block 2360. The reagent tray 2365 may be any suitable tray, etc. For example, the reagent tray 2365 may hold and / or otherwise define a set of wells 2366 configured to receive any suitable solution, fluid, gel, lysate, buffer, sample, analyte, amphoteric electrolyte, drug, reagent, protein, substrate, etc. In other embodiments, the wells 2366 may receive one or more vials 2367, etc., which can contain any of the samples and / or mixtures described herein. The wells 2366 can be of any preferred shape, size, or configuration and can be arranged in any preferred arrangement. For example, the wells 2366 can be a well plate, a microwell plate, etc. As shown in Figure 12, the reagent tray 2365 contains 42 wells 2366. In other embodiments, the reagent tray can contain any number of wells (e.g., 43 or more wells or less than 42 wells). In some embodiments, the reagent tray 2365 is removably coupled to the tray holder 2362 so that a reagent tray having any preferred number and / or arrangement of wells can be coupled to the tray holder 2362 at least temporarily. Furthermore, as will be described in more detail herein, the drive unit 2310 of the reagent assembly 2300 moves the tray unit 2340 within the housing 2100 to selectively fluidize one or more wells 2366 of the reagent tray 2365 to a portion of the cartridge retainer 2400 and / or a cartridge 2500 located within the cartridge retainer 2400.

[0088] The cooler 2350 of the tray section 2340 is coupled to the tray holder 2362. The cooler 2350 may be any suitable device, mechanism, assembly, etc. configured to transfer thermal energy to or from the cooler 2350. For example, as shown in Figure 12, the cooler 2350 includes a fluid block 2351 and a thermoelectric cooling device 2355. The fluid block 2351 has an inlet 2352 configured to receive a fluid inlet flow into the fluid block 2351 and an outlet 2353 configured to receive a fluid outlet flow from the fluid block 2351. As shown in Figure 13, the fluid block 2351 is fluidically coupled to a pump 2385, which is further fluidically coupled to a heat exchanger 2390 (e.g., a shell-and-tube heat exchanger, a radiator, etc.). Thus, the pump 2385 can receive a flow of a relatively hot or heated fluid (e.g., water, coolant, etc.) from the outlet 2353 of the fluid block 2351 and pump a certain amount of fluid into the heat exchanger 2390. The heat exchanger 2390 includes and / or is coupled to a fan 2395 configured to supply a flow of bulk fluid (e.g., air) across the outer surface of the heat exchanger 2390, thereby removing thermal energy from the fluid flowing within the heat exchanger 2390. The relatively cold or cooled fluid can then flow into the inlet 2352 of the fluid block 2351. Therefore, the fluid flowing through the fluid block 2351 can be configured to transfer thermal energy to or from the fluid block 2351.

[0089] The thermoelectric cooling device 2355 (also referred to herein as the “cooling device”) may be any suitable cooling device, such as a Peltier element configured to produce a temperature gradient in response to an electrical input (e.g., voltage or a change in voltage). In some embodiments, the cooling device 2355 has a high-temperature surface that is in thermal communication with at least the fluid flowing through the fluid block 2351 and a low-temperature surface that is in thermal communication with at least the cold block 2360. Thus, the cooling device 2355 can receive a current flow (e.g., from the power supply 2210 of the electronic assembly 2200) that is operable to produce a temperature gradient between the low-temperature and high-temperature surfaces of the cooling device 2355. Thus, with the cold block 2360 in contact with the reagent tray 2365 (as described above), thermal energy can be transferred from the reagent tray 2365 through the cold block 2360 to the low-temperature surface of the cooling device 2355, and through the cooling device 2355 to the fluid flowing in the fluid block 2351. Subsequently, as described above, at least some of the thermal energy is removed from the fluid as it flows through the heat exchanger 2390. Thus, the tray portion 2340 of the reagent assembly 2300 can cool, chill, and / or otherwise regulate the sample and / or other mixture in the reagent tray 2365.

[0090] Alternatively, the hot side of the cooling device 2355 can be thermally connected to the cold block 2360, and the cold side of the cooling device 2355 can be thermally connected to the fluid passing through the fluid block 2351, thereby enabling the cooling device to operate to transfer thermal energy to the reagent tray 2365 (for example, to operate to function as a heater). For example, by changing the polarity of the voltage applied to the cooling device 2355, the cooling device 2355 may be operated to alternate between being a heating device and a cooling device. In some cases, a control device, such as a proportional-integral-derivative (PID) control device, may be operated to change the polarity, duty cycle, duration, potential, etc., supplied to the cooling device 2355 in order to maintain the temperature of the reagent tray 2365 within a specific temperature range. In some embodiments, such a control device may be and / or include a set of instructions stored in memory and executed in the processor of the PCBA 2212 of the electronic assembly 2200.

[0091] The capillary cartridge retainer 2400 (also referred to herein as the “cartridge retainer”) of system 2000 is located within the housing 2100. For example, as shown in Figure 14, a portion of the cartridge retainer 2400 is fixedly coupled to the optical support member 2121 of the frame 2120. Thus, at least a portion of the cartridge retainer 2400 is maintained in a substantially fixed position within the housing 2100. More specifically, as will be described in further detail herein, a portion of the cartridge retainer 2400 is coupled to the optical support member 2121 and maintained within a range of fixed positions relative to the detection assembly 2700, thereby maintaining a desired alignment between them.

[0092] The cartridge retainer 2400 may be any preferred shape, size, or configuration. For example, as shown in Figures 15 to 20, the cartridge retainer 2400 includes a frame 2410, a vacuum section 2440, a latch mechanism 2455, and a pipette section 2470. As will be described in more detail herein, the frame 2410 is configured to couple the cartridge retainer 2400 to the optical support member 2121 and to accept and selectively engage with at least a portion of the cartridge 2500. Furthermore, as shown in Figures 15 to 18, each of the vacuum section 2440, the latch mechanism 2455, and the pipette section 2470 is coupled to and / or otherwise supported by the frame 2410.

[0093] As shown in Figures 15 and 16, the pipette section 2470 includes a pipette 2481 coupled to a side wall of the frame 2410 (for example, a second side wall 2421 as described in further detail herein) and configured to move linearly relative to the frame 2410. The pipette section 2470 further includes a mounting block 2471, a motor 2472, a rack 2473, a pinion 2474, a belt 2475, a support member 2476, a slide track 2478, and a slide block 2479. The mounting block 2471 and the support member 2476 are configured to be coupled to the second side wall 2421 of the frame 2410, respectively. The motor 2472 is coupled to the mounting block 2471 and includes an output section (not shown). The output section of the motor 2472 is operatively coupled to the pinion 2474 via the belt 2475. The pinion 2474 is rotatably coupled to the mounting block 2471 and is configured to rotate by the belt 2475 in response to the rotation of the output section of the motor 2472. The rack 2473 is configured to move linearly relative to the mounting block 2471, engaging with the gears (not shown) of the pinion 2474. As shown in Figure 16, the ends of the rack 2473 and the pipette 2481 are coupled to the slide block 2479. The slide block 2479 is slidably positioned around a portion of the slide track 2478, which is coupled to a support member 2476 and is further configured to be maintained in a position substantially fixed relative to the frame 2410. Furthermore, as will be described in more detail herein, the support member 2476 defines a notch 2477 configured to movably receive a portion of the latch mechanism 2455.

[0094] This arrangement of the pipette section 2470 causes the belt 2475 to rotate the pinion 2474 relative to the rack 2473 when the motor 2472 is activated. With the pinion 2474 rotatably coupled to the mounting block 2471 and the gear portion of the pinion 2474 engaged with the rack 2473, the rotation of the pinion 2474 causes the rack 2473 to advance relative to the pinion 2474. With the end of the rack 2473 coupled to the slide block 2479, the advance of the rack 2473 relative to the pinion 2474 results in linear motion of the slide block 2479 along the length of the slide track 2478. Therefore, with the pipette 2481 coupled to the slide block 2479, the pipette 2481 moves simultaneously with the slide block 2479 as the slide block 2479 moves along the length of the slide track 2478. In this way, the electronic assembly 2200 can send signals and / or power to the motor 2472 to move the pipette 2481 linearly along the length of the slide track 2478 (for example, along the length of the centerline defined by the pipette 2481).

[0095] In some cases, the pipette 2481 can be moved from a first position to a second position so that it is positioned in one or more wells 2366 of the reagent tray 2365. For example, the motor 2472 can be actuated (e.g., depending on a signal and / or power received from the electronic assembly 2200) so that the first end of the pipette 2481 is positioned in a well 2366 of the reagent tray 2465. Furthermore, as shown in Figure 16, the second end of the pipette 2481 opposite the first end 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 well 2366 in which it is positioned. For example, in some embodiments, one or more fluid conduits 2480 are in fluid communication with a pump 2490, etc. (see, for example, Figure 13). The pump 2490 is further in fluid communication with at least one fluid reservoir 2495. Thus, the electronic assembly 2200 and / or other control devices can signal the pipette assembly 2470 to actuate the motor 2472 so that the first end of the pipette 2481 is positioned in the desired well 2366. The electronic assembly 2200 can also signal the pump 2490 (e.g., a syringe pump or other suitable pump) so that the pump 2490 can draw a predetermined amount of fluid from one or more fluid reservoirs 2495 and deliver a predetermined amount of fluid to the well 2366 via one or more fluid conduits 2480 and pipette 2481. In some embodiments, this arrangement allows the system 2000 to fill and / or otherwise prepare one or more wells 2366 of the reagent tray 2365 with a desired sample or mixture, such as those described herein, at least semi-automatically.

[0096] In some embodiments, the fluid reservoir 2495 may be sized to accommodate relatively small amounts of fluid, such as 20 milliliters (mL), 50 mL, or 100 mL. The fluid reservoir 2495 can store enough fluid for one or more runs (e.g., two, five, or ten runs). Optionally, the interior of the housing 2100 can be air-conditioned so that the fluid reservoir 2495 is maintained at a preset and / or substantially constant temperature. For example, fans 2215 and / or 2395 can be circulated so that heat generated from system components (e.g., electrical components, power supplies, transformers, cooling devices 2355, etc.) is dissipated at a controlled rate to maintain a preset and / or substantially constant temperature. The fluid reservoir 2495 may be sized to accommodate relatively small amounts of fluid, and the temperature of such fluid can be controlled more easily than, for example, a multi-liter bulk fluid reservoir.

[0097] Depending on the circumstances, the fluid reservoir 2495 may be fluidically coupled to a bulk fluid container (not shown) located, for example, outside the housing 2100. The fluid reservoir 2495 may be operable to draw fluid from and / or receive fluid from the bulk fluid container. In some embodiments, the filling level of a bulk fluid container having a known volume can be determined by supplying a known amount of gas to the bulk fluid container at a known pressure. By calculating the change in pressure within the bulk fluid container (for example, the volume of headspace in the fluid reservoir 2495 and / or the bulk fluid container; i.e., the change in pressure within the bulk fluid container decreases as the headspace increases), the filling level can be calculated by subtracting the headspace from the known volume of the bulk fluid container. In some embodiments, the system 2000 may prompt the user to refill one or more bulk fluid containers and / or otherwise modify the behavior of the run when the filling level drops below a predetermined level (for example, the system 2000 may prevent the assay from being performed until the bulk fluid containers are refilled).

[0098] The frame 2410 of the cartridge retainer 2400 can be any preferred shape, size, and / or configuration. As shown in Figures 16 to 19, for example, 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 positioned between the first side wall 2411 and the second side wall 2421, respectively, and are configured to connect 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 connected to the side walls 2411 and 2421 and positioned between them such that the first side wall 2411 and the second side wall 2421 are spaced a predetermined distance apart (see, for example, Figure 19). In some embodiments, the predetermined distance may relate, for example, to the width of the cartridge 2500. In other words, the first contact bracket 2438 and the second contact bracket 2439 are coupled together such that the side walls 2411 and 2421 are joined so that a space sufficient to accommodate at least a portion of the cartridge 2500 is defined between them. 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 contacts a portion of the cartridge 2500 when the cartridge 2500 is positioned between the second side wall 2421 and the first side wall 2411.

[0099] As shown in Figure 17, the first sidewall 2411 defines one or more spring openings 2412, a first optical system opening 2414, and a second optical system opening 2415. The first optical system opening 2414 is configured to align with a first part of the optical system assembly 2700 (e.g., the size imaging unit 2701, as further described herein) so as to enable visualization of a first part of the cartridge 2500 when the cartridge 2500 is held by the cartridge retainer 2400. Similarly, the second optical system opening 2415 is configured to align with a second part of the optical system assembly 2700 (e.g., the whole column detection unit 2750, as further described herein) so as to enable visualization of a second part of the cartridge 2500 when the cartridge 2500 is held by the cartridge retainer 2400.

[0100] One or more spring openings 2412 defined by the first side wall 2411 are configured to receive portions of a spring 2450. For example, as shown in Figure 17, the first side wall 2411 defines two spring openings 2412 that receive different portions of the spring 2450. The spring 2450 (e.g., a leaf spring) may be a relatively thin, elongated member that can be bent, deformed, biased, and / or otherwise reconfigured, and such a member can exert a reaction force accordingly. In this way, by positioning portions of the spring 2450 within the spring openings 2412, the spring 2450 can be configured in a biased state that converts potential energy into kinetic energy in response to a force applied to at least a portion of the spring 2450. As shown, the spring 2450 includes a roller 2451 located at the end of the spring 2450 that contacts the surface of the cartridge 2500 when the cartridge 2500 is inserted into the cartridge retainer 2400. In some embodiments, the cartridge 2500 applies a force to the spring 2450 that is sufficient to bias or temporarily deform the spring 2450 when it comes into contact with the roller 2451.

[0101] As shown in Figures 18 and 19, the second side wall 2421 has an inner surface 2427 that includes and / or forms a first guide rail 2428 (e.g., an upper guide rail) and a second guide rail 2429 (e.g., a lower guide rail). The first guide rail 2428 and the second guide rail 2429 are configured to selectively engage with, guide and / or support the relevant portion of the cartridge 2500 when the cartridge 2500 is placed in the space defined between the first side wall 2411 and the second side wall 2421. More specifically, the first guide rail 2428 and the second guide rail 2429 may engage with and / or guide the portion of the cartridge 2500 to ensure that the cartridge 2500 is held in a desired position and / or orientation within the cartridge retainer 2400. For example, in some embodiments, the alignment of the cartridge 2500 within the cartridge retainer can have a tolerance of 1.0 micron (μm) to approximately 500 μm (0.5 millimeters (mm)) or less.

[0102] As described in more detail herein, the second side wall 2421 defines a latch opening 2422, a vacuum motor opening 2423, a first optical system opening 2424, a second optical system opening 2425, and a notch 2426. The notch 2426 defined by the second side wall 2421 is configured to receive a portion of the optical system support member 2121 of the frame 2120 and / or otherwise positioned around it, in order to facilitate the coupling of the cartridge retainer 2400 to the optical system 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 respect to the first sidewall 2411, the first optical system aperture 2424 and the second optical system aperture 2425 of the second sidewall 2421 are configured to align with the first and second portions of the optical system assembly 2700, respectively, so as to enable visualization of the first and / or second portions of the cartridge 2500 when the cartridge 2500 is held by the cartridge retainer 2400. Furthermore, at least the second optical system aperture 2425 may include and / or receive a focusing lens 2405 and / or any other suitable optical component.

[0103] The second side wall 2421 also includes and / or is coupled to the shaft 2430 and the engaging member 2431. The shaft 2430 is an elongated member having a first end movably coupled to and / or movably positioned within the second side wall 2421, and a second end opposite the first end, coupled to the engaging member 2431. The shaft 2430 is configured to move relative to the second side wall 2421 in response to an applied force. For example, in some embodiments, the reagent tray 2365 can be moved vertically so that a portion of the reagent tray 2365 and / or sample vials contained within the reagent tray 2365 come into contact with the engaging member 2431. Thus, further movement of the reagent tray 2365 (in the same direction) applies a force to the engaging member 2431 that is sufficient to move the shaft perpendicular to the second side wall 2421. More specifically, in some embodiments, a portion of the shaft 2430 is movably positioned within an opening defined by the second side wall 2421. In these embodiments, the force applied to the engaging member 2431 may be sufficient to increase the portion of the shaft 2430 positioned within the opening, thereby compressing the shaft 2430 extending from the second side wall 2421 and / or otherwise shortening its length. In some embodiments, the arrangement of the shaft 2430 and the engaging member 2431 may be configured to restrict the vertical movement of the reagent tray 2365, thereby substantially preventing damage to the cartridge 2500 and / or cartridge retainer 2400 that could otherwise occur if they were not present. In other embodiments, the shaft 2430 and / or the engaging member 2431 may include and / or be operably coupled to a sensor (e.g., a proximity sensor, pressure sensor, accelerometer, etc.) configured to detect and / or sense the position and / or force relating to the movement of the shaft 2430 (and / or reagent tray 2365) relative to the cartridge retainer 2400.Therefore, based at least partially on the data detected and / or requested by these sensors, the system 2000 can control the movement of the reagent tray 2365 and / or any other suitable part of the system 2000 relative to the cartridge retainer 2400.

[0104] As described above, the vacuum section 2440 and the latch mechanism 2455 are coupled to the frame 2410. As shown in Figures 16 to 19, the vacuum section 2440 of the cartridge retainer 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 2442 and a second end 2443. The first end 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 pin (see, for example, Figure 17). The second end 2443 of the lever arm 2441 is coupled to a connector 2446, etc., configured to connect and / or couple the second end 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 output members extend through the vacuum motor opening 2423 (see, for example, Figure 18) and connect to the connector 2446. Thus, the connector 2446 operably connects the lever arm 2441 to the motor 2447. In this way, the motor 2447 can rotate its output section in response to signals and / or power (e.g., sent from the electronic assembly 2200), thereby causing the lever arm 2441 to rotate and / or pivot about an axis defined by the first end 2442 (e.g., about a pin, axle, pivot point, etc.).

[0105] The pinch valve actuator 2444 and the pressure nozzle 2445 are each coupled to the lever arm 2441 and configured to move with the lever arm 2441 in response to the operation of the motor 2447. More specifically, the pinch valve actuator 2444 is coupled to and / or otherwise located there or near the second end 2443 of the lever arm 2441, while the pressure nozzle 2445 is located closer to and / or substantially in the center 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 with a predetermined portion of the cartridge 2500 when the cartridge 2500 is held by the cartridge retainer 2400 and the motor 2447 is operated to rotate the lever arm 2441. For example, in some embodiments, the pinch valve actuator 2444 may be configured to drive a pinch valve contained in the cartridge 2500 to control the flow of fluid through one or more fluid passages. Similarly, the pressure nozzle 2445 may be configured to engage with and / or drive a portion of the cartridge 2500 configured to regulate the pressure in one or more fluid passages and / or capillaries. For example, the pressure nozzle 2445 may be fluidically coupled (e.g., via any suitable fluid conduit, tube, pipe, etc.) to a pump 2497, etc., which can be actuated to generate positive pressure. Thus, as described in further detail herein, the pressure nozzle 2445 may engage with a portion of the cartridge 2500 to transmit at least a portion of the positive pressure to that portion of the cartridge 2500.

[0106] As shown in Figures 17 and 19, the vacuum port 2448 is coupled to the first contact bracket 2438. As will be described in more detail herein, the vacuum port 2448 is configured to engage and / or contact a portion of the cartridge 2500 when the cartridge 2500 is positioned within the cartridge retainer 2400. Not shown, the vacuum port 2448 can be coupled to any suitable fluid conduit, tube, pipe, etc., thereby providing fluid communication between the vacuum port 2448 and a vacuum source. For example, a fluid conduit, etc., can be configured to provide fluid communication between the vacuum port 2448 and a vacuum source 2496 (see, for example, Figure 13). The vacuum source 2496 may be any suitable device, etc., configured to provide a negative differential pressure between the vacuum source 2496 and, for example, the vacuum port 2448. In some embodiments, the vacuum source 2496 may include an impeller, etc., configured to rotate within a chamber to generate negative pressure. In other embodiments, the vacuum source 2496 may be a piston pump or other suitable pump. Thus, as will be described in more detail herein, when the cartridge 2500 is in contact with the vacuum port 2448, the vacuum source 2496 can be activated (for example, depending on the signals and / or power received from the electronic assembly 2200) to generate a negative pressure within a portion of the cartridge 2500.

[0107] The latch mechanism 2455 of the cartridge retainer 2400 may be any preferred member, device, mechanism and / or assembly. For example, as shown in Figures 16, 18 and 19, the latch mechanism 2455 includes a latch arm 2456, a motor 2459 and a manual release member 2465. The latch arm 2456 may be any preferred shape, size and / or configuration. The first end of the latch arm 2456 is configured to be coupled to the output (not shown) of the motor 2459 such that the rotation of the output brings about a similar and / or corresponding rotation of the latch arm 2456. As shown in Figures 18 and 19, the latch arm 2456 includes a pin 2457 and a latch member 2458. The pin 2457 is configured to contact a fastener and / or a portion of the frame 2410 to restrict the rotation of the latch arm 2456. The latch member 2458 is coupled to the end of the latch arm 2456 opposite to the end coupled to the motor 2459. The latch member 2458 may be any preferred pin, roller, knob, tab, projection, etc., configured to selectively engage with a portion of the cartridge 2500 when the cartridge 2500 is positioned within the cartridge retainer 2400, as described in further detail herein.

[0108] The latch member 2458 is operable to ensure that the cartridge 2500 is reliably positioned with high precision and repeatability relative to the first contact bracket 2438 and the second contact bracket 2439. Thus, the latch member 2458, the guide rails 2428 and 2429, and the contact brackets 2438 and 2439 together can align the cartridge 2500 when it is inserted into the cartridge retainer 2400. In some cases, it may be desirable to have precise control over the direction and / or alignment of the insertion of the cartridge 2500 (e.g., insertion of the cartridge 2500 into the cartridge retainer 2400) to ensure alignment with the optical system assembly 2700. Depending on the configuration, the latch member 2458, guide rails 2428 and 2429, and contact brackets 2438 and 2439 may be operable to reproducibly position the cartridge 2500 within a tolerance range of, for example, 0.1 mm, 0.05 mm, 0.01 mm, 0.005 mm, or any other preferred distance. Furthermore, the cartridge retainer 2400 may include one or more sensors 2488 (see, for example, Figure 19) configured to detect and / or sense the position or alignment of the cartridge 2500 within the cartridge retainer 2400. For example, the sensor 2488 may be a proximity sensor and / or any preferred switch, plunger, actuator (e.g., mechanical and / or electrical), etc. In some embodiments, when the cartridge 2500 is positioned in the desired location within the cartridge retainer 2400, the sensor 2488 may send a signal to the motor 2459 indicating a command to rotate the latch arm 2456.

[0109] The manual release member 2465 includes a first end 2466, a second end 2467, and a contact portion 2468. The first end 2466 of the manual release member 2465 is rotatably coupled to the second side wall 2421 of the frame 2410, as shown in Figure 18. Furthermore, a portion of the manual release member 2465 is movably positioned within a notch 2477 defined by the support member 2476. The second end 2467 is opposite to the first end 2466 and can be engaged and / or operated by the user to pivot and / or rotate the manual release member 2465 around an axis defined by the first end 2466 (e.g., a pin, screw, axle, coupling, bearing, etc.). Furthermore, when the manual release member 2465 rotates around the axis defined by the first end 2466, the contact portion 2468 contacts the pin 2457 of the latch arm 2456. In this way, the user can apply force to the second end 2467 of the manual release member 2465 to bring the contact portion 2468 into contact with the pin 2457 of the latch arm 2456, thereby allowing the latch arm 2456 to rotate and / or pivot relative to the frame 2410. Therefore, in the event of a motor failure, the cartridge 2500 can be manually released from the cartridge retainer 2400.

[0110] The optical system assembly 2700 of system 2000 is housed within the housing 2100 and coupled to the optical system support member 2121 of the frame 2120. More specifically, the optical system assembly 2700 can be housed within the housing 2100 so as to at least partially surround the cartridge retainer 2400. As shown in Figures 20 to 28, the optical system assembly 2700 includes a single-point detection unit 2701 (Figures 20 to 23) and a whole-column detection unit 2750 (Figures 24 to 28). The single-point detection unit 2701 may have any preferred shape, size, and / or configuration. As shown in Figure 20, the single-point detection unit 2701 is coupled to the cartridge retainer 2400 and / or otherwise positioned around it in a predetermined position, such that one or more of its components are substantially aligned with the first optical system openings 2414 and 2424 of the first side wall 2411 and the second side wall 2421, respectively, enabling the single-point detection unit 2701 to perform molecular weight analysis on a sample flowing through the cartridge 2500 (e.g., molecular weight cartridge 2500'). As will be described in more detail herein, the whole column detection unit 2750 is positioned around the cartridge retainer 2400 in a predetermined position, such that one or more of its components are substantially aligned with the second optical system openings 2415 and 2425 of the first sidewall 2411 and the second sidewall 2421, respectively, enabling the whole column detection unit 2750 to detect the movement of analytes (e.g., proteins) along the length of the capillary 2500 (e.g., isoelectric focusing electrophoresis cartridge 3500'') before, during, and / or after separation.

[0111] As shown in Figures 21 to 23, the single-point detection unit 2701 includes an illumination assembly 2705, a central member 2710, a first lateral member 2720 coupled to a first imaging device 2725, and a second lateral member 2730 coupled to a second imaging device 2735. Furthermore, as will be described in more detail herein, the single-point detection unit 2701 may include any number of filters, lenses, holders, mirrors, etc., configured to direct at least a portion of the light emitted from the illumination assembly 2705.

[0112] The lighting assembly 2705 includes an inlet block 2706 and an optical fiber member 2707 (also referred to herein as the “optical output unit”). The inlet block 2706 is coupled to the side of the central member 2710 and further coupled to the optical output unit 2707. Thus, as will be described in more detail herein, the inlet block 2706 can direct and / or guide a beam of light (e.g., photons) emitted from the optical output unit 2707 into one or more bores defined by the central member 2710. The optical output unit 2707 can be optically coupled to a light source 2795 (see, for example, Figure 13), such as a deuterium lamp, incandescent lamp, LED, or any other suitable optical fiber light source, which can be excited and / or otherwise actuated in response to signals and / or power received from an electronics assembly 2200 (e.g., a power supply 2210) and / or any other suitable control device. In some embodiments, the optical output unit 2707 can be configured to emit energy and / or photons generated by a light source 2795 having a desired wavelength (e.g., wavelengths such as the infrared spectrum, visible light spectrum, ultraviolet spectrum, etc.).

[0113] The central member 2710 can be of any shape, size, and / or configuration. For example, as shown in Figures 22 and 23, the central member 2710 defines a central bore 2711, a side bore 2712, a cartridge retainer notch 2713, a mirror notch 2714, and a filter notch 2715. The central bore 2711 has a substantially circular cross-sectional shape and extends laterally along the length of the central member 2710. In this embodiment, the central bore 2711 receives, for example, a filter holder 2743 that holds or includes three lenses 2741, a mirror 2742, and a filter 2744. More specifically, the central bore 2711 has a first lens 2741 positioned adjacent to the entrance block 2706 of the illumination assembly 2705, a second lens 2741 positioned adjacent to and on the first side of the cartridge retainer notch 2713, and a third lens 2741 positioned adjacent to and on the second side of the cartridge retainer notch 2713 opposite to the first side (see, for example, Figure 23). As described in further detail herein, the mirror 2742 is positioned within the mirror notch 2714, which positions the mirror 2742 in a desired position so as to direct at least a portion of the light emitted from the light output section 2707 towards the side bore 2712. The filter holder 2743 is positioned within the filter notch 2715, which positions the filter 2744 (held and / or coupled to the filter holder 2743) at a desired position between the first lens 2741 and the side bore 2712. In this way, the first lens 2741 can focus at least a portion of the light emitted from the optical output section 2707, and furthermore, the filter 2744 can filter that portion of the light before it enters the rest of the side bore 2712 and / or the central bore 2711 (see, for example, Figure 23).

[0114] Referring again to Figure 20, the single-point detection unit 2701 of the optical system assembly 2700 is positioned relative to the cartridge retainer 2400 such that at least a portion of the cartridge retainer 2400 is positioned within a cartridge retainer notch 2713 defined by the central member 2710. More specifically, the single-point detection unit 2701 and the cartridge retainer 2400 are collectively positioned such that the central bore 2711 of the central member 2710 is substantially aligned with portions of the first optical system apertures 2414 and 2424 defined by the first sidewalls 2411 and second sidewalls 2421 of the frame 2410, respectively. In this way, the lens 2741, filter 2744, and mirror 2742 positioned within the central bore 2711 collectively direct the focused and filtered portion of the light emitted by the optical output unit 2707 to pass through a predetermined portion of the cartridge retainer 2400. Therefore, as will be described in more detail herein, when the cartridge 2500 is held by the cartridge retainer 2400, the focused and filtered portion of the light also passes through a predetermined portion of the cartridge 2500.

[0115] The first lateral member 2720 of the single-point detection unit 2701 defines a bore 2721 and a notch 2722. The first lateral member 2720 is coupled to the central member 2710 such that its bore 2721 is substantially aligned with the lateral bore 2712 of the central member 2710. The bore 2721 of the first lateral member 2720 receives and / or accommodates the lens 2741. In this way, the mirror 2742 positioned within the central bore 2711 of the central member 2710 can direct at least a portion of the light emitted by the light output unit 2707 into the bore 2721 of the first lateral member 2720, and that portion of the light is then focused by the lens 2741 positioned within the bore 2721.

[0116] The first lateral member 2721 is also coupled to the first imaging device 2725 (see, for example, Figure 21). The first imaging device 2725 includes a thermal-mass reference member 2726, a shielding material 2727, and a photodiode printed circuit board assembly (PCBA) 2728. As shown in Figure 22, the thermal-mass reference member 2726 is positioned within the shielding material 2727, which shields (e.g., insulates) the thermal-mass reference member 2726. The shielding material 2727 and the thermal-mass reference member 2726 are positioned within a notch 2722 defined by the first lateral member 2722 (e.g., between the first lateral member 2722 and the photodiode PCBA 2728). The thermal-mass reference member 2726 may be any suitable device, sensor, etc. The thermal-mass reference member 2726 may be configured to maintain the first imaging device 2725 at a substantially constant and / or reference temperature. The photodiode PCBA 2728 (also referred to herein as the “photodiode”) may be any suitable device configured to detect and / or sense an input of light (e.g., photons) and convert the input into an electric current. Thus, the photodiode 2728 can generate signals related to the scattering of light emitted by the light output unit 2707 and / or an image of a certain amount of sample flowing through the capillary of the cartridge 2500. These signals can be interpreted by a processor (e.g., of the electronics assembly 2200) to determine characteristic molecular weight, electrophoretic mobility, morphology, etc., of the analytes in the sample. While described as a photodiode, in other embodiments the single-point detection unit 2701 may include any suitable imaging device, such as a CCD camera.

[0117] The second lateral member 2730 of the single-point detection unit 2701 includes a mirror block 2740 configured to be coupled to and / or to hold the mirror 2742, defining a bore 2731 and a notch 2732. The second lateral member 2730 is coupled to and / or positioned adjacent to the central member 2710. As shown in Figure 21, the arrangement of the single-point detection unit 2701 is such that the first lateral member 2720 is coupled to and / or positioned on the first side of the cartridge retainer notch 2713, and the second lateral member 2730 is coupled to and / or positioned on the second side of the cartridge retainer notch 2713 opposite to the first side. Furthermore, the second lateral member 2730 is positioned relative to the central member 2710 such that a portion of the light emitted from the optical output section 2707 is redirected by the mirror 2742 into the bore 2731 defined by the second lateral member 2730, and thereby focused by one or more lenses 2741 positioned within the bore 2731.

[0118] As described above with respect to the first lateral member 2720, the second lateral member 2730 is also coupled to the second imaging device 2735 (see, for example, Figure 21). The second imaging device 2735 includes a thermal mass reference member 2736, a shielding material 2737, and a photodiode PCBA 2738. The second imaging device 2735 may be substantially similar to the first imaging device 2725 described above and is therefore not described in detail herein.

[0119] The first imaging device 2725 and the second imaging device 2735 can individually and / or collectively generate signals (e.g., electronic signals containing data and / or information) relating to the generation, scattering, and / or absorption of light in both forward and backward directions, which are influenced by a certain amount of analyte, standard material, labeled portion, etc., in the sample flowing through the capillary of cartridge 2500. For example, the first imaging device 2725 may be operable to detect light emitted, scattered, and / or absorbed from a dark-field and / or rear-viewpoint (e.g., from approximately 95 to 265 degrees opposite the beam direction), and the second imaging device 2735 may be operable to detect light emitted, scattered, and / or absorbed from a bright-field and / or forward-viewpoint (e.g., from approximately 85 to 275 degrees in the beam direction). Thus, the single-point detection unit 2701 of system 2000 may be operable to detect, for example, when an analyte separated by molecular weight and / or electrophoretic mobility flows through a portion of the capillary of cartridge 2500, as will be described in more detail herein. The molecular weight of each analyte can be determined based on the time and / or sequence in which it is detected. For example, an analyte detected after a 10,000 Da standard but before a 15,000 Da standard can be determined to have a molecular weight of 10,000 to 15,000. The molecular weight can be determined more accurately by considering the timing between the detection of the 10,000 Da standard, the analyte, and the 15,000 Da standard.

[0120] The all-column detection unit 2750 of the optical system assembly 2700 may be any suitable device, mechanism, subassembly, etc. As described above with respect to the single-point detection unit 2701, the optical system assembly 2700 is arranged within the housing 2100 such that the all-column detection unit 2750 surrounds at least a portion of the cartridge retainer 2400. As will be discussed in more detail herein, the all-column detection unit 2750 and the single-point detection unit 2701 of the optical system assembly 2700 can each surround a portion of the cartridge retainer 2400, for example, so that any imaging mode can be used depending on the configuration of the cartridge 2500 inserted into the cartridge retainer 2400.

[0121] As shown in Figures 24 to 28, the total column detection unit 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 an output of light energy. As shown in Figures 25 and 26, for example, the illumination 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 the “optical output unit”) may be any suitable radiator (e.g., a light or photon radiator). For example, in some embodiments, the optical output unit 2752 may be an array of optical fiber output units configured to radiate light energy generated by a light source (e.g., light source 2795). In some embodiments, the optical output unit 2752 may be an array of LEDs, etc. In yet another embodiment, the optical output unit 2752 may be a single radiator configured to radiate light through an elongated aperture, etc., defined by the optical output unit 2752. In this way, the optical output unit 2752 can output, for example, a light stream having a predetermined length.

[0122] In some embodiments, the optical output unit 2752 can output light energy and / or photons having wavelengths such as ultraviolet spectrum. In some embodiments, the optical output unit 2752 may be a narrowband light source and / or can generate a stream of light having a single wavelength. In other embodiments, the optical output unit 2752 may include a filter or monochromator configured to output a stream of light having a single wavelength. Thus, the optical output unit 2752 can emit photons having a desired wavelength and / or energy (e.g., ultraviolet wavelength or energy) that are absorbed by one or more analytes, standards, fluorescent labels, etc. in the sample contained in the capillary of the cartridge 2500. Furthermore, as will be described in more detail herein, one or more analytes, standards, labels, etc., can therefore emit one or more photons (e.g., via fluorescence, phosphorescence, etc.) which are detected by the imaging assembly 2760.

[0123] Depending on the circumstances, the optical output unit 2752 may be operable and / or optimized for whole-column and / or real-time detection. For example, the optical output unit 2752 may be an LED array configured to output a relatively constant optical output over a relatively long period of time compared to, for example, a laser light source. More specifically, some known electrophoresis methods use a laser to illuminate a single point on the column with high intensity for a relatively short period of time. While such methods are suitable for delivering sufficient energy to a single point to achieve accurate measurements, the intensity of the laser can damage the detector if applied for a long period of time, so these methods are generally not suitable for whole-column detection or real-time detection. However, an LED array can illuminate the entire column with lower intensity for a longer period of time to generate sufficient energy to achieve accurate measurements of the entire column while electrophoresis is occurring.

[0124] The mounting structure 2753 includes a first adjustment block 2754, a second adjustment block 2755, an adjustment plate 2756, and a pair of mounting clamps 2758. The mounting clamps 2758 are coupled to the end of the adjustment plate 2756 to tighten, connect, and / or otherwise hold the lens 2759 in a fixed position relative to the end of the adjustment plate 2756, as shown in Figure 25. The mounting structure 2753 is configured to flexibly support the optical output unit 2752 and / or to flexibly mount to, for example, the optical system support plate 2121 of the frame 2120. More specifically, as shown in Figure 26, the mounting structure 2753 includes a first mounting plate 2757 configured to flexibly connect the first adjustment block 2754 to the second adjustment block 2755, and a second mounting plate 2757 configured to flexibly connect the second adjustment block 2755 to the adjustment plate 2756. In some embodiments, the mounting structure 2753 is arranged such 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 cartridge retainer 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 cartridge retainer 2400). Similarly, the light output unit 2752 can be slidably coupled to the adjustment plate 2756 so that it can be slid along the length of the adjustment plate 2756 to be positioned, for example, closer to or further away from the lens 2759. Thus, the light output unit 2752 can be positioned in a desired position relative to the cartridge retainer 2400 and / or the cartridge 2500 held by the cartridge retainer 2400, as described in further detail herein.

[0125] The imaging assembly 2760 of the whole-column detection unit 2750 may be and / or include any suitable device, mechanism, assembly, etc. As shown in Figures 27 and 28, the imaging assembly 2760 includes an imaging device 2761, a seal bracket 2762, one or more seals 2763, a rotating flange 2765, and a transition flange 2767. The imaging device 2761 may be any suitable camera or detector configured to detect signals emitted by the analyte and / or standard material (as described above). The imaging device 2761 may be, for example, a charge-coupled device (CCD) array, etc., which can be used to continuously monitor signals emitted by the analyte and / or standard material in real time, enabling a user to quickly determine whether or not an analyte is present in a sample and, optionally, the quantity or activity of the analyte. In other embodiments, the imaging device 2761 may be a photodiode, such as the photodiodes 2728 and 2738 described above.

[0126] The seal bracket 2762, seal 2763, rotating flange 2765, and transition flange 2767 are collectively configured to couple the imaging device 2760 to the mounting block 2771 of the focusing assembly 2770. Furthermore, the arrangement of the imaging assembly 2760 is such that the imaging device 2761 is isolated from light emitted by an external light source (e.g., other than the optical output unit 2752). In other words, the seal bracket 2762, seal 2763, rotating flange 2765, and transition flange 2767 collectively form an opaque seal between the imaging device 2761 and the mounting block 2771.

[0127] The focusing assembly 2770 includes a mounting block 2771, a lens holder 2774, a lens 2775, a mirror retaining block 2776, a motor 2781, and a filter wheel 2784. As described above, the mounting block 2771 is coupled to the imaging assembly 2760 (e.g., the transition flange 2767 or other part of the imaging assembly 2760). The mounting block 2771 is also coupled to the mirror retaining block 2776 (see, for example, Figure 27). In other words, the mounting block 2771 is positioned between the imaging assembly 2760 and the mirror retaining block 2776. The mounting block 2771 can be any preferred shape, size, and / or configuration. For example, as shown in Figure 28, the mounting block 2771 defines an aperture 2772 and a motor recess 2773. The lens holder 2774 receives the lens 2775 and is movably positioned within the aperture 2772. The motor 2781 is at least partially positioned within the motor recess 2773 (see, for example, Figure 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 may be configured to rotate a pinion, etc., so that a rack included in and / or formed by the lens holder 2774 can advance relative to the pinion. Thus, the lens holder 2774 can be moved within the mounting block 2771 to focus at least a portion of the light passing through the lens 2775 (e.g., radiated by the optical output unit 2752).

[0128] As described above, the mirror retaining block 2776 is coupled to the mounting block 2771. The mirror retaining block 2776 defines an opening 2778 and includes a mirror adjustment mechanism 2777. More specifically, the mirror adjustment mechanism 2777 is positioned within the opening 2778 defined by the mirror retaining block 2776 (see, for example, Figure 27). The mirror adjustment mechanism 2777 is configured to receive and / or couple to the mirror 2790 and can be engaged, operated and / or otherwise reconfigured to adjust and / or move the mirror 2790 within the mirror retaining block 2776. The arrangement of the whole column detection unit 2750 is such that the opening 2778 defined by the mirror retaining block 2776 is aligned with, for example, the second optical system openings 2415 and 2425 of the first sidewall 2411 and second sidewall 2421 of the cartridge retainer 2400, respectively. Thus, the light emitted from the optical output unit 2752 can enter the aperture 2778 defined by the mirror holding block 2776 through the second optical system apertures 2415 and 2425 of the cartridge retainer 2400 (and a portion of the cartridge 2500 located therein). The mirror 2790 can then be adjusted and / or positioned to direct at least a portion of the light towards the imaging device 2761, as will be described in more detail herein.

[0129] The filter wheel 2784 is operably coupled to the motor 2781 (for example, via one or more gears 2782) and rotatably positioned between the mounting block 2771 and the mirror holding block 2776. The filter wheel 2784 can be any preferred shape, size and / or configuration. For example, as shown in Figure 28, the filter wheel 2784 is a relatively thin plate defining a set of apertures 2785. More specifically, in this embodiment, the filter wheel 2784 defines a set of six apertures 2785, each of which is configured to receive an optical filter, etc. (not shown). The optical filter can be any preferred filter, lens and / or other optical device configured to focus, filter, convert and / or otherwise modify at least a portion of the passing light. In some embodiments, each aperture 2785 defined by the filter wheel 2784 may contain a different filter and / or lens. Thus, the motor 2781 can rotate the filter wheel 2784 to align any one of the filters with the aperture 2772 defined by the mounting block 2771. Therefore, at least a portion of the light directed towards the imaging device 2761 by the mirror 2790 passes through the desired filter (and lens 2776) before entering the imaging device 2761, as will be described in more detail herein.

[0130] In some cases, the filter wheel 2784 can be rotated during the electrophoresis run. In this way, a different imaging mode can be used while the electrophoresis process is taking place. For example, the filter wheel 2784 can be positioned in a first position so that the first filter is aligned with the opening 2772 defined by the mounting block 2771, and then moved (e.g., rotated) to the second, third, and / or fourth positions so that the second, third, and / or fourth filters are aligned with the opening 2772, respectively. In some of these cases, the first filter may allow the imaging device 2761 to capture fluorescence induced in a labeled portion bound to the analyte, the second filter may allow the imaging device 2761 to capture the intrinsic fluorescence of the first analyte, the third filter may allow the imaging device 2761 to capture the intrinsic fluorescence of the second analyte, and the fourth filter may allow the imaging device 2761 to detect the absorbance of the analyte. In other embodiments, the filter wheel 2784 may include any other suitable filter or combination of filters. By rotating the filter wheel 2784, another image of the entire column (illuminated by, for example, the light output unit 2752) can be acquired at any point during the run. In this way, the fluorescence of the label, the intrinsic fluorescence of the analyte, and / or the absorbance of the analyte can be tracked separately in a single run as the analyte moves through the column (e.g., the capillary).

[0131] As described above, the system 2000, specifically the cartridge retainer 2400, can be configured to receive different cartridges such as the molecular weight cartridge 2500' and the isoelectric focusing cartridge 2500''. Other types of cartridges, such as isokinetic electrophoresis cartridges and capillary electrochromatography cartridges, are also possible. In some cases, the cartridge 2500 may be reusable. Similarly, the cartridge 2500 may be suitable for performing multiple analyses with the same or different samples.

[0132] As shown in Figures 29 to 37, the molecular weight cartridge 2500' has a cartridge body 2501' and a capillary 2530'. The cartridge body 2501' defines at least one aperture 2505', at least one vertical alignment feature 2510' and at least one horizontal alignment feature 2515'. As described above with respect to Figures 18 and 19, the vertical alignment feature 2510' can be configured to slidably engage, fit, and / or interact with a first guide rail 2428 (e.g., upper guide rail) and a second guide rail 2429 (e.g., lower guide rail) of the cartridge retainer 2400. More specifically, in this embodiment, the cartridge body 2501' includes a first vertical alignment feature (e.g., an upper alignment feature) configured to engage with a first guide rail 2428, and a second vertical alignment feature (e.g., a lower alignment feature) configured to engage with a second guide rail 2429. In some embodiments, the vertical alignment feature 2510' may be, for example, a groove, notch, slot, channel, etc., configured to receive a portion of the first guide rail 2428 or the second guide rail 2429 (see, for example, Figures 29, 33, and 34). Thus, the guide rails 2428 and 2429 and the vertical alignment feature 2510' collectively restrict and / or substantially prevent the vertical movement of the molecular weight cartridge 2500'.

[0133] The horizontal alignment feature 2515' can similarly be configured to engage with the latch member 2458 of the cartridge retainer 2400. For example, the horizontal alignment feature 2515' may be a notch, groove, slot, channel, etc., configured to selectively receive and contact a portion of the latch member 2458 when the latch member 2458 moves into a latched or locked position, as shown in Figures 33 and 34. The horizontal alignment feature 2515' may have a V-shape so that the latch member 2458 can be rotated into the surface of the cartridge body 2501' defining the horizontal alignment feature 2515' and locked to it. In this way, the horizontal alignment feature 2515' and the latch member 2458 together can prevent the horizontal movement (e.g., in the insertion direction) of the molecular weight cartridge 2500'. Furthermore, as will be described in more detail herein, when the latch member 2458 engages with the horizontal alignment feature 2515', the molecular weight cartridge 2500' can be drawn into the cartridge retainer 2400 such that one or more portions of the molecular weight cartridge 2500' contact the contact member 2485. In some embodiments, the latch member 2458 can be moved to contact the horizontal alignment feature 2515' in response to the surface of the cartridge body 2501' contacting the sensor 2488. In some embodiments, the cartridge body 2501' can 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 retainer 2400 to prevent the molecular weight cartridge 2500' from moving in a horizontal direction other than the insertion direction of the cartridge 2500' (e.g., transverse or lateral). Thus, the cartridge retainer 2400 can limit and / or substantially prevent the horizontal and / or vertical movement of the molecular weight cartridge 2500' relative to the cartridge retainer 2400 when the latch member 2458 is engaged.

[0134] One or more apertures 2505' defined by the cartridge body 2501' may be any preferred shape, size, or configuration, as shown in Figures 29 to 31, for example. The molecular weight cartridge 2500' includes a first aperture 2505' located on the first side of the cartridge body 2501' and a second aperture 2505' located on the second side opposite to the first side of the cartridge body 2501'. More specifically, the first aperture 2505' and the second aperture 2505' are located in opposite and / or aligned positions. The position of the aperture 2505' is such that, when the molecular weight cartridge 2500' is placed in the cartridge retainer 2400, the aperture 2505' is substantially aligned with, for example, the central bore 2711 of the central member 2710 included in the single-point detection unit 2701 of the optical system assembly 2700. Furthermore, the capillary 2530' is positioned within the cartridge body 2501' such that a portion of the capillary 2530' is aligned with and / or between the aperture 2505' (see, for example, Figures 29 and 30), thereby allowing a portion of the capillary 2501' to be visualized by the single-point detection unit 2701 of the optical system assembly 2700.

[0135] The capillary 2530' can be configured to fluidly communicate with a sample contained in a sample vial 2367 placed in a reagent tray 2365, for example. In some embodiments, the end 2532' of the capillary 2530' can extend outside the cartridge body 2501' of the molecular weight cartridge 2500'. In other embodiments, the capillary 2530' can fluidly communicate with a sample in one or more sample vials 2367 and / or wells 2366 via a pipette tip or other suitable structure protruding from the cartridge body 2501'. In some embodiments, a sleeve 2535', such as a plastic or carbon sleeve, can be placed around a portion of the capillary 2530' to improve its rigidity, for example. In this way, the sleeve 2535' can protect the end 2532' of the capillary 2530' and prevent its undesirable deformation or breakage. Such a sleeve 2535' can be rigid enough to, for example, puncture a partition or other cover of a sample vial. In some embodiments, the sleeve 2535' can further provide shielding (e.g., thermal insulation and / or thermal insulation) to the end 2532' of the capillary 2530'.

[0136] The molecular weight cartridge 2500' also includes a pressure line 2550', a pressure port 2551', and a seal 2552', as shown in Figures 31-35. When the molecular weight cartridge 2500' is placed in the cartridge retainer 2400, the pressure line 2550' can be fluidly coupled to the pressure nozzle 2445 via the pressure port 2551' (see, for example, Figure 35). The seal 2552' is configured to press against the sample vial 2367 or container as the reagent tray 2365 moves relative to the molecular weight cartridge 2500'. For example, the reagent tray 2365 can be configured to move vertically so that the seal 2552' contacts the sample vial, thereby fluidly communicating the capillary 2530' with the sample vial. The system 2000 can be configured to pressurize the sample vial and activate a pressure source 2497 that can push the sample out of the vial into the capillary 2530'. Alternatively, the capillary 2530' can be fluidly coupled to the vacuum source 2496 via the vacuum port 2448 and the vacuum interface 2541'. The system 2000 can be configured to operate the vacuum source 2496 and / or the pressure source 2497 to push the sample flow from the vial into the capillary 2530'. By applying both negative and positive pressure to the sample vial, a certain amount and / or flow rate of sample having a desired set of characteristics (e.g., less bubbles, turbulence, etc.) can be drawn into the capillary 2530'.

[0137] The molecular weight cartridge 2500' further comprises a double-walled vial 2540' having an inlet septum 2543' and an outlet septum 2542' (see, for example, Figures 31 and 35). The inlet septum 2543' and / or the outlet septum 2542' may be substantially impermeable to liquid. The inlet septum 2543' is perforated by the end 2531' (opposite end 2532') of the capillary 2530', so as to allow the capillary 2530' to fluidly and electrically communicate with the internal volume of the double-walled vial 2540'. For example, the double-walled vial 2540' can contain a working buffer that can be delivered to the capillary 2530' and / or can receive and store waste samples from the capillary 2530' during the current run or a preceding run. Furthermore, at least one end 2531' of the capillary 2530' is conductive, and therefore, when the end 2531' punctures the inlet stub 2543', the capillary 2530' is electrically connected or electrically coupled to the double-stub vial 2540'.

[0138] In some embodiments, the outlet partition 2542' may be gas permeable, thereby allowing air, rather than liquid, to be pushed through the outlet partition 2542' as the sample is drawn into the double-walled vial 2540' through the capillary 2530'. Furthermore or alternatively, the double-walled vial 2540' may contain a sponge, filter, and / or other absorbent material to prevent the sample from escaping from the molecular weight cartridge 2500'. In this embodiment, the outlet partition 2542' is perforated by a vacuum interface 2541'. Optionally, once the run is complete, the system 2000 may be configured to dry the double-walled vial 2540', for example, by circulating air through the double-walled vial 2540'. In some embodiments, the system 2000 may be configured to track and / or determine the amount of sample aspirated into the double-walled vial 2540' and to warn the user to replace the double-walled vial 2540' and / or molecular weight cartridge 2500' when the double-walled vial 2540' is full and / or after a predetermined number of runs. Optionally, the system 2000 may be configured to shut down at least some of its operations when the double-walled vial 2540' is full.

[0139] The double-walled vial 2540' is configured to be electrically coupled to at least a portion of the system 2000 when the molecular weight cartridge 2500' is placed within the cartridge retainer 2400'. For example, when the molecular weight cartridge 2500' is held by the cartridge retainer 2400, a portion of the contact member 2485 extending from the first contact bracket 2438 is positioned to contact the double-walled vial 2540' within the molecular weight cartridge 2500'. 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 electrically contacts the double-walled vial 2540' with the voltage (or current) source. Similarly, a contact member 2485 extending from the second contact bracket 2439 can be brought into contact with a portion of the molecular weight cartridge 2500' and / or a portion of the capillary 2530' to establish an electrical connection between them. Therefore, a potential can be applied to the capillary 2530' via the contact bracket 2485 and the double-walled vial 2540', thereby inducing an electromotive force in the analyte within the capillary 2530'. If the analyte is charged, the potential can attract the analyte to the end 2531' of the capillary 2530' (e.g., towards the double-walled vial 2540'). In some cases, the analyte and / or other parts of the sample may flow toward the end of the capillary 2530' with a set of properties (e.g., mobility parameters, etc.), at least partially based on molecular weight, where analytes with smaller molecular weights may move faster than analytes with larger molecular weights.

[0140] As shown in Figures 35 to 37, the molecular weight cartridge 2500' can be placed in the cartridge retainer 2400, and the system 2000 can be configured to perform molecular weight analysis. If necessary, the user may prepare the reagent tray 2365 and / or the molecular weight cartridge 2500' before inserting the molecular weight cartridge 2500'. Then, as described above, the user can insert the molecular weight cartridge 2500' into the cartridge retainer 2400 in a single predetermined orientation. In this way, the molecular weight cartridge 2500' can be positioned in the desired location within the cartridge retainer 2400, thereby aligning the aperture 2505' with the single-point detection optical system 2701, as shown in Figure 37. More specifically, the molecular weight cartridge 2500' is placed in the system 2000 such that the aperture 2505', and therefore the capillary 2530', is aligned with the central bore 2711 of the central member 2710. Therefore, by aligning the molecular weight cartridge 2500' with the single-point detection optical system unit 2701, the energy and / or photons emitted by the optical output unit 2707 can be directed to a predetermined portion of the capillary 2530'.

[0141] Once the molecular weight cartridge 2500' is held within the cartridge retainer 2400, the reagent tray 2365 can be moved relative to the molecular weight cartridge 2500' so as to position at least a portion of the capillary 2530' within the wells and / or sample vials of the reagent tray 2365, as described above. Furthermore, the capillary 2530' is fluidly coupled to the vacuum source 2496 once the molecular weight cartridge 2500' is positioned within the cartridge retainer 2400. This thereby allows the vacuum source 2496 to be activated (e.g., at least semi-automatically) within the capillary 2530' to generate a negative differential pressure capable of drawing the sample into the capillary 2530'. When the capillary 2530' is placed in the well and / or sample vial, the contact member 2485 can transfer electrical energy (e.g., current) to the double-walled vial 2540' and a portion of the molecular weight cartridge 2500' and / or capillary 2530', thereby applying a potential to the sample, resulting in the movement of analytes within the sample. The rate at which the analytes move within the capillary 2540' can be correlated with one or more mobility coefficients, such as molecular weight.

[0142] Thus, as the analyte moves within the capillary 2530', the light output unit 2707 can emit energy or photons, thereby illuminating and / or exciting a certain amount of sample flowing through a predetermined portion of the capillary 2530' (to which the energy or photons are directed). Subsequently, the photodiodes 2728 and 2738 capture and / or detect at least a portion of the energy and / or photons reflected, refracted and / or absorbed by the illuminated and / or excited analyte, standard substance, labeled portion, etc., in their respective capacities of sample. The photodiodes 2728 and 2738 can then transmit signals containing data related to and / or the detection, and the system 2000 (e.g., the processor of the electronics assembly 2200) can analyze the data to obtain molecular weight-based data and / or electrophoretic mobility data related to the analyte in the sample. For example, the length of time between the applied potential and the detected analyte can be correlated with the molecular weight and / or mobility coefficient of the analyte. In other embodiments, the flow of the sample can be guided by a vacuum source 2496 and / or a pressure source 2497.

[0143] While System 2000 has been described above as accepting a molecular weight cartridge 2500' and performing molecular weight analysis, in other cases, System 2000 can accept an isoelectric focusing electrophoresis cartridge 2500'' and be configured to perform electrophoresis followed by visualization and detection. As shown in Figures 38 to 44, the isoelectric focusing electrophoresis cartridge 2500'' has a set of cartridge body 2501'', a capillary 2530'', and an electrode 2560''. The cartridge body 2501'' defines at least one aperture 2505'', at least one vertical alignment feature section 2510'', and at least one horizontal alignment feature section 2515''. The vertical alignment feature section 2510'' and the horizontal alignment feature section 2515'' may be the same as those described above with respect to the molecular weight cartridge 2500'. Thus, the isoelectric focusing electrophoresis cartridge 2500'' can be similarly positioned and temporarily fixed within the cartridge retainer 2400.

[0144] The aperture 2505'' defined by the cartridge body 2501'' can be any preferred shape, size, and / or configuration. For example, as shown in Figures 38 to 41, the aperture 2505'' is an elongated opening located on the opposite side of the cartridge body 2501'' (as described above with respect to the molecular weight cartridge 2500''). Thus, when the isoelectric focusing cartridge 2500'' is placed inside the aperture 2505'', the aperture 2505'' can be optically aligned with the second optical apertures 2415 and 2425 of the cartridge retainer 2400. Furthermore, the aperture 2505'' may allow optical access to the length of the capillary 2530'', thereby enabling the full column detection unit 2750 of the optical assembly 2700 to image the sample before, during, and / or after isoelectric focusing. The aperture 2505'' and the all-column detection unit 2750 of the optical system assembly 2700 can be configured collectively to perform all-column imaging. Similarly, the aperture 2505'' can expose substantially the entire length (e.g., more than 90% of the length) of the capillary 2530'' positioned between the electrodes 2560''.

[0145] The isoelectric focusing electrophoresis cartridge 2500'' further includes a slit plate 2520''. The slit plate 2520'' can be optically aligned with the aperture 2505'' and / or the capillary 2530''. The slit plate 2520'' can improve the resolution of the isoelectric focusing image, for example, by reducing the lens effect associated with the curvature of the capillary 2530''. Similarly, the slit plate 2520'' can expose the center of the capillary 2530'' to the full column detection section 2750 of the optical system assembly 2700 while closing the edge 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 preferred slit width.

[0146] As shown in Figures 40 and 41, the isoelectric focusing electrophoresis cartridge 2500'' includes a capillary 2530'', a pressure line 2550'', a pressure port 2551'', a seal 2552'', and a sleeve 2535'', each of which may be structurally and / or functionally similar to the capillary 2530'', pressure line 2550'', pressure port 2551'', seal 2552'', and sleeve 2535'' described above with respect to the molecular weight cartridge 2500''. Thus, a sample from one or more vials 2367 or wells 2366 of the reagent tray 2365 can be aspirated into the capillary 2530'' in the same manner as described above with respect to the molecular weight cartridge 2500''. The isoelectric focusing electrophoresis cartridge 2500'' can be configured to analyze a sample with substantially no bulk fluid flow. Thus, once a sample is aspirated into the capillary 2500'', bulk fluid flow can be blocked, as will be described in further detail herein.

[0147] As shown in Figures 40 to 44, the isoelectric focusing electrophoresis cartridge 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 cartridge body 2501'' is configured to receive the pinch valve actuator 2444 described above with respect to the vacuum section 2440 of the cartridge retainer 2400. The vacuum line 2572'' is fluidly coupled to the top of the capillary 2530''. When a sample is drawn into the capillary 2530'', the lever arm 2441 of the cartridge retainer 2400 can be rotated so that the pinch valve actuator 2444 applies force to the vacuum line 2572''. This force can deform the vacuum line 2572'' relative to 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, it can block or obstruct the bulk fluid flow within the capillary 2530''. In some cases, the pinch valve assembly 2570'' can be closed while a vacuum is applied, thereby creating negative pressure on the top of the capillary 2530''. Such negative pressure can counteract and / or overcome gravity. Similarly, the negative pressure applied to the pinch valve assembly 2570'' and / or the capillary 2530'' can block or obstruct bulk fluid movement within the vertical column under gravity.

[0148] Although not shown, the isoelectric focusing electrophoresis cartridge 2500'' may include a double-walled vial fluidly coupled to the capillary 2530'', similar to the double-walled vial 2540'' of the molecular weight cartridge 2500''. The double-walled vial 2540'' can contain a working buffer, such as a solution with a relatively high or low pH. The bottom septum may be configured to allow ion flow between the working buffer and the capillary 2530'' while blocking and / or limiting bulk fluid flow. In this way, the double-walled vial can create a pH gradient within the capillary 2530''.

[0149] In addition to the double-walled vial, the isoelectric focusing electrophoresis cartridge 2500'' includes a waste container 2540''. The waste container 2540'' can also be fluidically coupled to the capillary 2530''. Similarly, the waste container 2540'' may be fluidly parallel to the double-walled vial. The waste container 2540'' may contain a sponge, filter, or other suitable material. Once the run is complete, the pinch valve assembly 2570'' can be opened, allowing the sample to be aspirated into the waste container 2540'' via the vacuum source 2496. For example, the bottom partition of the double-walled vial may direct the sample into the waste container 2540'' and prevent the fluid sample from being drawn out of the cartridge 2500''. In some embodiments, the waste container 2540'' can function similarly to the waste container 2540'' contained in the molecular weight cartridge 2500''.

[0150] The isoelectric focusing electrophoresis cartridge 2500'' further includes a set of electrodes 2560''. In this embodiment, the set of electrodes 2560'' includes two electrodes. Electrodes 2560'' can be configured to contact a corresponding contact member 2485 when the isoelectric focusing electrophoresis cartridge 2500'' is placed in the cartridge retainer 2400 (Figure 44). The contact member 2485 can then be electrically coupled to a voltage (or current) source, such as a power supply 2210 of an electronic equipment assembly 2200. The two electrodes 2560'' are also electrically coupled to the capillary 2530'' and / or the sample in the capillary 2530''. For example, in some embodiments, as shown in Figure 44, the capillary 2530'' may be conductive, with a first end 2531'' electrically coupled to the first electrode 2560'' and a second end 2532'' electrically coupled to the second electrode 2560''. In some embodiments, one electrode 2560'' can be coupled to the double-walled vial described above. In such embodiments, the double-walled vial may be conductive so that the working buffer in the double-walled vial can be electrically coupled to the electrode 2560''. The system 2000 can be configured to operate the power supply 2210 so that a potential is induced along the capillary 2530'' containing the sample. The potential allows the analytes in the sample to move to their isoelectric points along the pH gradient in the capillary 2530'', as described in detail above.

[0151] As described above with respect to the molecular weight cartridge 2500'', the user can place the isoelectric focusing cartridge 2500'' in the cartridge retainer 2400 and set the system 2000 to, for example, an electrophoresis analysis setting and / or configuration. If necessary, the user can prepare the reagent tray 2365 and / or the isoelectric focusing cartridge 2500'' before inserting the isoelectric focusing cartridge 2500''. As described above, the user can then insert the isoelectric focusing cartridge 2500'' into the cartridge retainer 2400 in a single predetermined orientation. Thus, as shown in Figure 42, the isoelectric focusing cartridge 2500'' can be placed in a desired position within the cartridge retainer 2400 so that the aperture 2505'' is aligned with the entire column detection unit 2750 of the optical system assembly 2700. More specifically, the isoelectric focusing electrophoresis cartridge 2500'' is positioned within the system 2000 such that the aperture 2505'', and therefore the capillary 2530'', are aligned with the second optical system apertures 2415 and 2425 of the cartridge retainer 2400, the light output unit 2752, and the aperture 2778 of the mirror holding block 2776. Thus, by aligning the isoelectric focusing electrophoresis cartridge 2500'' with the whole column detector 2750, the energy and / or photons emitted by the light output unit 2752 can be directed to a predetermined portion of the capillary 2530''.

[0152] Once the isoelectric focusing cartridge 2500'' is held within the cartridge retainer 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'' within the wells and / or sample vials of the reagent tray 2365, as described above. Furthermore, when the isoelectric focusing cartridge 2500'' is positioned within the cartridge retainer 2400, the capillary 2530'' is fluidically coupled to the vacuum source 2496. Thus, the vacuum source 2496 can then be activated (e.g., at least semi-automatically) to generate a negative differential pressure capable of drawing in the amount of sample contained within the capillary 2530''.

[0153] Once a mixture containing the desired components (e.g., a sample) is drawn into the capillary 2530'', the system 2000 can, for example, activate the vacuum section 2440 of the cartridge retainer 2400 to insert at least a portion of the pinch valve actuator 2444 into the pinch valve opening 2520'' of the cartridge body 2501'' and bring it into contact with the pinch valve assembly 2570'' of the isoelectric focusing electrophoresis cartridge 2500''. Thus, the pinch valve actuator 2444 can close the pinch valve assembly 2570'' by deforming a portion of the vacuum line 2572'' relative to the pinch plate 2571'', as described above. With the pinch valve assembly 2570'' in the closed position, the bulk fluid flow through the capillary 2530'' is limited, restricted, and / or substantially blocked. Subsequently, the system 2000 can apply an electric field to the capillary 2530'' by, for example, supplying a current flow to the contact member 2485. Therefore, with the contact member 2485 in contact with the electrode 2560'', the current also flows through the electrode 2560'', resulting in a voltage difference between the ends 2531'' and 2532'' of the capillary 2530''. Thus, depending on the current supplied to the capillary 2530'', as described in detail above, the analytes in the sample are moved and / or separated along the length of the capillary 2530'' according to the isoelectric point of each analyte, etc.

[0154] Depending on the circumstances, the whole-column detection unit 2750 can detect a "whole-column" image or signal and / or perform "whole-column" detection of the sample within the capillary 2530''. Similarly, the imaging device 2761 may be operable to capture more than a single point along the capillary 2530''. For example, the imaging device 2761 may be operable to capture and / or detect a length sufficient to visualize the separation and / or focus of the analyte during the electrophoresis process (e.g., about 1 cm, about 3 cm, about 5 cm, about 10 cm, about 20 cm, about 50 cm, or any other suitable length of the capillary 2530''). Furthermore or alternatively, the imaging device 2761 may be operable to capture and / or detect the intrinsic fluorescence and absorbance of the analyte within the capillary 2530''. For example, while the analyte is being separated and / or focused within the capillary 2530'', the filter wheel 2784 can be rotated to modify the optical signal presented to the imaging device 2761. Thus, while the analyte is being separated and / or focused during a single run, the sample can be characterized for intrinsic fluorescence, absorbance, and / or other suitable optical properties along the entire column.

[0155] In some embodiments, reagents, reagent trays, capillary cartridges, etc., can be packaged separately or collectively as a kit for analyte detection using any of the systems or methods described herein. In some embodiments, the kit may include materials that provide molecular weight, isoelectric point, and / or any other suitable standard substance as described herein. Furthermore, one or more mobility parts, one or more reactive parts, one or more labeling parts can be packaged individually or collectively. In some embodiments, the kit may include one or more electrophoretic standards containing peptides, one or more fluorescent dyes, and one or more photoreactive groups. Furthermore, buffers, polymeric materials or polymerizable materials, blocking solutions, and washing solutions can be packaged together with the reagents, reagent trays, capillary cartridges, etc., or packaged separately from the reagents, reagent trays, capillary cartridges, etc. The components can be provided separately or mixed together in dry or liquid form.

[0156] Some embodiments described herein relate to computer storage products that include a non-temporary computer-readable medium (which may also be called a processor-readable medium) having instructions or computer code for performing various computer operations. A computer-readable medium (or processor-readable medium) is non-temporary in the sense that it does not contain inherently temporary propagating signals (e.g., propagating electromagnetic waves that carry information in a transmission medium such as space or a cable). The medium and computer code (which may also be called code) may be designed and configured for one or more specific purposes. Examples of non-temporary computer-readable mediums 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 discs (CDs / DVDs), compact disk read-only memory (CD-ROMs) and holographic devices; magneto-optical storage media such as optical disks; carrier signal processing modules; and hardware devices specifically configured to store and execute program code, such as application-specific integrated circuits (ASICs), programmable logic devices (PLDs) and read-only memory (ROM) and random access memory (RAM) devices. Other embodiments described herein relate, for example, to computer program products that may include instructions and / or computer code considered herein.

[0157] Some embodiments and / or methods described herein can be implemented by software (executed in hardware), hardware, or a combination thereof. Hardware modules include, for example, general-purpose processors, field-programmable gate arrays (FPGAs), and / or application-specific integrated circuits (ASICs). Software modules (executed in hardware) can be represented in various software languages ​​(e.g., computer code), including C, C++, Java®, Ruby, Visual Basic®, and / or other object-oriented, procedural, or other programming languages ​​and development tools. Examples of computer code include, but are not limited to, files containing microcode or microinstructions generated by a compiler, machine instructions, code used to create web services, and high-level instructions executed by a computer using an interpreter. For example, embodiments can be implemented using imperative programming languages ​​(e.g., C, FORTRAN, etc.), functional programming languages ​​(e.g., Haskell, Erlang, etc.), logic programming languages ​​(e.g., Prolog), object-oriented programming languages ​​(e.g., Java, C++, etc.), or other suitable programming languages ​​and / or development tools. Further examples of computer code include, but are not limited to, control signals, encryption codes, and compression codes.

[0158] While various embodiments have been described above, it should be understood that they are presented merely as examples and not as limitations. The schematic diagrams and / or embodiments described above show several components arranged in several orientations or positions, but the arrangement of components can be changed. While some embodiments have been specifically illustrated and described, it will be understood that various modifications can be made in form and detail. While various embodiments have been described as having specific features and / or combinations of components, other embodiments are possible having any combination of features and / or components from any of the embodiments described above.

[0159] If the methods and / or events described above describe several events and / or procedures that occur in a specific order, the order of some of the events and / or procedures can be changed. Furthermore, some events and / or procedures can be performed simultaneously in parallel processes where possible, as well as sequentially as described above.

Claims

1. Housing and A cartridge retainer disposed within the housing, comprising a first side and a second side, wherein the first and second sides are substantially parallel and define a space between them configured to receive at least a portion of a capillary cartridge, the first side defines a first opening and a second opening, the second side defines a first opening substantially aligned with the first opening of the first side, and the second side defines a second opening substantially aligned with the second opening of the first side, A light source disposed within the housing, configured to emit a first beam of light and a second beam of light, wherein at least a portion of the first beam of light is directed to pass through the first opening of the first side and the first opening of the second side, and at least a portion of the second beam of light is directed to pass through the second opening of the first side and the second opening of the second side, A detection assembly disposed within the housing, wherein the detection assembly is configured to transition between a first mode in which it detects light related to at least a portion of the first beam of light, and a second mode in which it detects light related to at least a portion of the second beam of light. A system that includes this.

2. The system according to claim 1, wherein the cartridge retainer is configured to receive at least one of a first capillary cartridge and a second capillary cartridge in the space defined between the first side and the second side, the first beam of light is configured to illuminate a portion of the capillary of the first capillary cartridge when the cartridge retainer receives the first capillary cartridge, and the second beam of light is configured to illuminate a portion of the capillary of the second capillary cartridge when the cartridge retainer receives the second capillary cartridge.

3. The system according to claim 1, wherein the cartridge retainer is fluidly coupled to a pressure source, and the cartridge retainer is configured to fluidly communicate the capillary cartridge with the pressure source when at least a portion of the capillary cartridge is located in the space between the first side and the second side, and the pressure source is configured to selectively increase or decrease the pressure within a portion of the capillary cartridge.

4. The system according to claim 3, wherein the cartridge retainer includes a valve actuator, the valve actuator is configured to engage with a pinch valve of the capillary cartridge to move the pinch valve between a first and a second form, and bulk flow within the capillary of the capillary cartridge is substantially blocked when the pinch valve is in the second form.

5. The system according to claim 1, wherein the cartridge retainer includes a plurality of surfaces configured to contact the capillary cartridge when the capillary cartridge is positioned in the space defined between the first side and the second side.

6. The first opening on the first side and the first opening on the second side are substantially circles having a diameter. The system according to claim 1, wherein the second opening of the first side and the second opening of the second side are substantially elongated openings having length and width, the length of the second opening being greater than the width of the second opening.

7. The first side portion has an inner surface and an outer surface opposite to the inner surface, and the second side portion has an inner surface and an outer surface opposite to the inner surface of the second side portion, and the inner surface of the first side portion and the inner surface of the second side portion define the space, The system according to claim 1, wherein the detection assembly includes a first portion adjacent to the outer surface of the first side and a second portion adjacent to the outer surface of the second side, the second portion of the detection assembly being spaced apart from the outer surface of the second side.

8. The system according to claim 1, further comprising a reagent tray holder movably disposed within the housing, configured to move relative to the cartridge retainer such that the capillary cartridge is positioned in the space defined between the first and second sides, thereby enabling fluid communication between the capillary of the capillary cartridge and the reagent volume.

9. The system according to claim 8, wherein the cartridge retainer includes an engaging portion, the engaging portion is configured to selectively contact the surface of the reagent tray holder when the reagent tray holder is moved relative to the cartridge retainer.

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