Cartridge Assembly

Abstract

You have a large system or multiple systems, or you need to run multiple sessions on a single system. [Solution] A cartridge assembly includes a housing including a flow cell chamber (108) that receives a flow cell, and a well plate having fluid wells that receive desired amounts of fluid. A pump assembly (500) controls fluid flow through a channel between a pump station and a fluid analysis station. A rotary valve assembly (200) includes a rotor shaft and a rotor valve mounted to rotate about an axis of rotation to selectively couple wells to the pump station. The rotor shaft includes a dual spline structure at its distal end. The dual spline structure has first and second sets of splines. The first set of splines forms a drive interface, and the second set of splines forms a position-encoding interface.

Description

[Technical field]

[0001] Related Applications This application is a continuation of U.S. Provisional Patent Application No. 62 / 408,631, filed December 14, 2016. No. 2017959 filed on 8 December 2016 and priority of Dutch patent application no. No. 60 / 313,939, filed on Oct. 13, 2007, which provisional application is hereby incorporated by reference in its entirety. [Background technology]

[0002] Many protocols used in biological or chemical research involve the performance of a number of control reactions. These reactions can be carried out, for example, in an automated system with appropriate fluidics, optics and electronics. These systems can be implemented according to a predetermined protocol, e.g. to generate biological or chemical products for subsequent use or to analyze the samples It can be used to detect some properties / characteristics of When analyzing samples using a chromatographic method, chemical moieties that contain distinguishable labels (e.g., fluorescent labels) are tested. The sample is then delivered to a chamber where it is placed and selectively bound to another chemical moiety in the sample. These chemical reactions can be performed by exciting the label with radiation and detecting the light emission from the label. Such light emission can be observed or confirmed by other means such as chemiluminescence. It can also be obtained by

[0003] Some known systems use a fluidic device such as a flow cell. The flow channel (eg, an internal chamber) is defined in one or more interior surfaces of the cell. Reactions can take place along the inner surface. Flow cells typically contain samples within a flow channel. The imaging device is disposed adjacent to an optical assembly that includes an objective lens. and / or a solid-state imager (e.g., CCD or CMOS). In this embodiment, no objective lens is used, and a solid-state imaging device is used to image the flow channel. The row cell is disposed immediately adjacent to the row cell.

[0004] Prior to imaging of the flow channel, it may be necessary to carry out a number of reactions with the sample. In sequencing by sequen- tion (SBS) technology, one or more surfaces of the flow channel are made of cross-linked PC The array of nucleic acid populations (e.g., clonal amplicons) formed by R. After generation of the acid population, the nucleic acid is "linearized" to obtain single-stranded DNA (sstDNA). To complete a sequencing cycle, multiple reaction components are run on a predefined schedule. Thus, the sstDNA flows into the flow channel. Add one or more nucleotides (e.g., A, T, G, C) to the flow cytometer to extend the sequence by a single base. The reversible terminator attached to the nucleotide is a single This ensures that only one nucleotide is incorporated per cycle by the sstDNA. Each nucleotide carries a unique fluorescent label that emits a color (e.g., red, green, blue, etc.) when excited. The newly incorporated nucleotides change the image of the nucleotide population into four groups. After imaging, different reaction components are added to the flow cytometer. The cleavage occurs in the sstDNA channel and chemically cleaves the fluorescent label and reversible terminator from the sstDNA. At this point, the sstDNA is ready for another cycle. Different reaction components are delivered to the flow channel for each cycle. A session may include many cycles, for example 100, 300 or more.

[0005] The fluids containing the reaction components are typically held in a reservoir (e.g., a tray or cartridge). Different fluids are held in different reservoirs. Multiple reaction components and multiple cycles Therefore, the total amount of fluid used during one session can be quite large. For some applications, it is impractical to deliver the entire amount of reaction components to a single cartridge. For such applications, it is possible to use large systems or multiple systems. or multiple sessions need to be run on a single system. This may be costly, inconvenient, or unreasonable in some environments.

[0006] definition All publications and similar materials cited in this application, including, but not limited to, patents, patent applications, Articles, books, monographs, web pages, etc., regardless of their format, may be incorporated by reference. No. 60 / 139,933, filed on Oct. 23, 2003, the entirety of which is expressly incorporated herein by reference. If one or more of the following are inconsistent with or in conflict with the present application,

[0007] As used herein, the following terms have the meanings indicated:

[0008] The embodiments described herein are directed to detecting a desired reaction of a sample in a biological or chemical assay. It includes various systems, methods, assemblies, and devices used for detection. In one embodiment, the desired response provides an optical signal that is detected by an optical assembly. The system may be light emission from a label or transmitted light reflected or refracted by the sample. For example, In some embodiments, sstDNA is sequenced in a flow cell. The present invention may be used to perform or facilitate the performance of a sensing protocol. In some embodiments, the embodiments described herein may be used to generate a sample of interest for sequencing. An amplification protocol may also be performed.

[0009] The embodiments described herein may have at least one of chemical, electrical, physical, and optical properties. It can produce a desired reaction that produces a change in the properties of a substance in response to a stimulus. For example, the desired reaction may be a chemical transformation, a chemical change, or a chemical interaction. In one embodiment, the desired response is detected by an imaging system. may include an optical assembly that directs the optical signal to a sensor (CCD or CMOS). However, in other embodiments, the imaging system may detect the optical signal directly. For example, the flow cell may be attached to a CMOS sensor. However, the desired response is For example, the desired reaction may be a change in the concentration of ions in a solution. good.

[0010] Representative reactions include, but are not limited to, chemical reactions, such as reduction, oxidation, addition, elimination, transformation, etc. , amidation, etherification, or substitution; a bonded phase where a first chemical entity is bonded to a second chemical entity. interactions; dissociation reactions in which two or more chemicals separate from each other; luminescence; chemiluminescence; etc.; and biology Biological reactions, such as nucleic acid replication, nucleic acid amplification, nucleic acid hybridization, nucleic acid ligation, etc. Desired reactions include catalysis, phosphorylation, enzymatic catalysis, receptor or ligand binding, etc. For example, the addition or removal of protons, which can be detected as a change in the pH of the surrounding solution or environment. Good too.

[0011] Various embodiments include providing a reaction component to the sample. "Component" or "reactant" includes any substance that can be used to effect a desired reaction. For example, Reaction components include reagents, enzymes, samples, other biomolecules, and buffer solutions. Reaction components are typically The reaction site includes the area where the sample is located, e.g., in solution or immobilized within the reaction site. ) The reaction component may interact directly or indirectly with the substance of interest.

[0012] In certain embodiments, the desired response is optically detected by an optical assembly. The assemblies communicate with each other to transmit the optical signal to an imaging device (e.g., CCD, CMOS or may include an optical train of optical elements directing the light to a photomultiplier tube (photomultiplier tube). The sample region is positioned directly adjacent to an active detector, which detects the desired reflection without the use of an optical train. An activity detector may detect a predetermined event, characteristic, or both within a predetermined volume or area. For example, an activity detector may detect an image of a given volume or area. The active detector may be capable of measuring the concentration of an ion in a given volume of solution or a given area. A typical active detector is a charge-coupled device (CC D) (e.g., CCD camera); photomultiplier tube (PMT) molecular characteristic device or detector; e.g., those using nanopores; microcircuitry, e.g., those incorporated herein in their entirety by reference; No. 7,595,883, incorporated herein by reference; and ion-sensitive field-effect transistor (chemFET), ion-sensitive field-effect transistor (Ion-Sensitive Field-Effect Transistor) Semiconductor Field Effect Transistors (ISFETs) and / or Metal Oxide Semiconductor Field Effect Transistors (MOTs) CMOS-made cell with field effect transistors (FETs) such as MOFETs Including sansa.

[0013] As used herein, "illumination elements" and "optical components" refer to any device that affects the propagation of optical signals. For example, optical components redirect, filter, and The module may perform at least one of filtering, shaping, magnifying, or concentrating. The optical signals reflected include an optical signal upstream of the sample and an optical signal downstream of the sample. In this system, the upstream components include those that direct the excitation radiation to the sample, and the downstream The flow components include components that direct the emitted radiation from the sample. Components include, for example, reflectors, dichroics, beam splitters, collimators, lenses, etc. , filters, prisms, mirrors, detectors, etc. Optical devices such as double-pass filters, optical wedges, and components similar to those described herein. Also includes.

[0014] As used herein, "optical signal" or "light signal" includes electromagnetic energy that can be detected. The term includes light emissions from labeled biological or chemical agents, as well as optical agents. This includes the transmitted light refracted or reflected by the excitation radiation incident on the sample and the light provided by the sample. The optical or light signal containing the optical radiation being transmitted may have one or more spectral patterns. For example, More than one type of label can be excited in an imaging session. In some cases, different types of labels may be excited at different times with a common excitation light source or with different excitation light sources. can be excited simultaneously. Each type of label has a different spectral pattern than the other labels. For example, these spectral patterns may be The light beams may have different emission spectra. The optical signal can be detected separately from the other emission spectra. The optical radiation may be filtered to achieve this.

[0015] The lighting elements and / or optical components may be in fixed positions within an optical assembly, In this specification, the term "selectively" is used in conjunction with "movement." When the word is used, the phrase means that the position of the optical components is in a desired manner. At least one of the position and the orientation of the optical components may be changed. For example, in certain embodiments, the focusing of the optical imaging system can be varied. A rotating mirror is selectively moved to facilitate this.

[0016] An analytical procedure (also referred to as an imaging session) involves imaging at least a portion of a sample. A sample may be subjected to or exposed to multiple imaging sessions. For example, ,One sample can undergo two different imaging sessions, and in each imaging session In a particular embodiment, the method comprises: A first scan along at least a portion of the nucleic acid sample detects labels associated with nucleic acids A and C. and a second scan along at least a portion of the sample is capable of detecting nucleic acids G and T. In a sequencing embodiment, separate sessions are performed according to the sequencing protocol. The imaging occurs in separate cycles of a single imaging session, each of which may include one or more imaging sessions. In other embodiments, the detection of optical signals in different imaging sessions may be performed using different sample scans. The different samples may be of the same type (e.g., two microarray chips) or They may be of different types (eg, flow cells and microarray chips).

[0017] During the analysis procedure, the optical signal provided by the sample is observed. It can be used in conjunction with the embodiments described herein. The embodiment uses a "step-and-shoot" process to image multiple regions of a sample area individually. These embodiments may use epifluorescence imaging and total internal reflection fluorescence (T In another embodiment, the imaging system may be configured to perform at least one of: The sample imager is a scanning time delay integration (TDI) system. The line focus of the light is scanned across the sample by one or more line focussing techniques. Several methods of line scanning are described, for example, in U.S. Pat. No. 29,860 and U.S. Patent Publication No. 2009 / 0272914. and , each of which is incorporated herein by reference in its entirety. may include moving the point-like focusing region of the sample in a raster pattern across the sample. In embodiments, an imaging session may be performed without illumination, entirely based on the luminescence properties of labels within a sample (e.g., The method includes detecting light radiation generated based on the presence of radioactive or chemiluminescent compounds in the sample. In an alternative embodiment, the flow cell may include an imager (e.g. The image sensor may be mounted on a CCD or CMOS.

[0018] As used herein, the term "sample" or "sample of interest" refers to a sample that is capable of receiving an optical signal from The various materials or substances that are subjected to the imaging session are included in certain embodiments. The sample may contain a biological or chemical substance of interest, and may optionally be a biological or chemical The sample may include an optical substrate or support structure that supports the biological material. As used herein, the term "biological or chemical" refers to a molecule that is a biological or chemical entity. "Target material" refers to any of a variety of biological materials suitable for being imaged or examined with the optical systems described herein. For example, the biological or chemical substance may be a nucleotide. , nucleic acids, polynucleotides, oligonucleotides, proteins, enzymes, polypeptides, antibodies body, antigen, ligand, receptor, polysaccharide, carbohydrate, polyphosphate, nanopore, organelle , lipid layers, cells, tissues, organisms, and biological analogs or mimetics of the above-mentioned species. Other chemicals include labels that can be used for identification, e.g. For example, fluorescent labels and other labels described in more detail below.

[0019] Different types of samples contain different optical substrates or support structures that affect the incident light differently. In certain embodiments, the sample to be detected may be attached to one or more surfaces of a substrate or support structure. For example, the flow cell may include one or more flow channels. In the present invention, the flow channel can be separated from the surrounding environment by the top and bottom layers of the flow cell. Thus, the optical signal to be detected is projected from within the support structure and is reflected by materials with different refractive indices. For example, optical signals from the inner bottom surface of a flow channel can be detected. When detecting an optical signal from above the flow channel, the optical signal to be detected is deflected. A fluid having a refractive index, one or more flow cells having different refractive indices, and It can spread through the surrounding environment.

[0020] The systems and methods described herein detect specific target molecules in a sample in contact with a microarray. This can be used to detect the presence of a labeled target analyte, for example. Binding to specific probes on the microarray to incorporate or remove labels at the probe locations, can be determined based on the modification. / 0108867, 2003 / 0108900, 2003 / 0170684, As described in No. 2003 / 0207295 or No. 2005 / 0181394 Thus, microarrays can be used to identify or characterize targets in any one of several assays. each of which is incorporated herein by reference.

[0021] Additionally, the optical system described herein is incorporated by reference in its entirety in its entirety, as defined in "System and Device" filed on March 30, 2007. The present application is entitled "Evictions for Sequence by Synthesis" and is incorporated herein by reference in its entirety. Various components and assemblies described herein and / or filed on September 26, 200 The international publication "Fluorescence Excitation and Detection System and Method" was Various components and assemblies described in WO 2009 / 042862 The present invention may be constructed to include the above-mentioned assemblies, both of which are incorporated herein by reference in their entireties. In certain embodiments, the optical system is No. 7,329,860 and WO 2009 / 137435. This may include the various components and assemblies described herein, which are incorporated by reference. The optical system is described in U.S. patent application Ser. No. 12 / 638,738, the entire disclosure of which is incorporated herein by reference. 70, which is incorporated herein by reference. the entire content of which is incorporated herein by reference.

[0022] In certain embodiments, the methods and optical systems described herein are used for nucleic acid sequencing. For example, a sequencing-by-synthesis (SBS) protocol can be used. In SBS, multiple fluorescently labeled modified nucleotides are attached to the optical substrate. present on a surface (e.g., a surface that at least partially defines a channel in a flow cell) Sequencing multiple clusters of amplified DNA (potentially millions of clusters) The flow cell contains a nucleic acid sample for sequencing, and the flow cell The samples are placed in a suitable flow cell holder. The sequencing samples are individually separated. Single nucleic acid molecules separated from one another, an amplified population of nucleic acid molecules in the form of clusters, or one or more The nucleic acid may be in the form of a bead having attached thereto a molecule as described herein above. The nucleic acid can be sequenced adjacent to the unknown target sequence. The first SBS sequence may be prepared to include an oligonucleotide primer. To initiate the transcription cycle, one or more differentially labeled nucleotides and DNA fragments are introduced. The polymerase or the like is flowed into / through the flow cell by a fluid flow subsystem (not shown). A single type of nucleotide may be added at a time, or the sequencing process may be The nucleotides used in the sequencer are specifically designed to have reversible termination properties. By this, each cycle of the sequencing reaction is enriched with several types of labeled nucleotides ( For example, A, C, T, G) can occur simultaneously. It can contain a detectable labeling moiety such as a fluorophore. When these nucleotides are mixed together, the polymerase will select and incorporate the correct base. Each sequence is extended by a single base. The nucleotides can be washed away by passing a wash solution through the flow cell. One or more lasers can excite the nucleic acid and induce fluorescence. The fluorescence emitted is based on the fluorophore of the incorporated base, and different fluorophores are A deblocking reagent can be added to the flow cell to generate light of different wavelengths. Reversible terminator groups can be removed from the extended and detected DNA strands. The deblocking reagent is then washed away by passing a wash solution through the flow cell. In this case, the flow cell can detect the amount of the labeled nucleotide as described above. The fluid is then ready for the next cycle of sequencing, which begins with the introduction. The tapping and detection steps can be repeated several times to complete a sequencing run. Exemplary sequencing methods are described, for example, in Bentley et al., Nature e456:53-59(2008); WO 04 / 018497; U.S. Pat. No. 7, No. 057,026; WO 91 / 06678; WO 07 / 123,744 U.S. Patent Nos. 7,329,492, 7,211,414, and 7, Nos. 3,315,019; 7,405,281; and U.S. Pat. No. 008 / 0108082, each of which is incorporated herein by reference. It can be seen.

[0023] In some embodiments, the nucleic acid is attached to a surface and amplified prior to or during sequencing. For example, amplification can be carried out using bridge amplification methods to form a population of nucleic acids on a surface. Useful bridge amplification methods are described, for example, in U.S. Pat. No. 5,641,658. Publication No. 2002 / 0055100; U.S. Patent No. 7,115,400 Publication No. 2004 / 0096853; Publication No. 2008 / 00094 Another useful method for amplifying nucleic acids on a surface is the rolling circle method. Recombinant Cyclic Amplification (RCA), see, for example, Lizardi et al., Nat. Genet. 19:225- 232 (1998) and US2007 / 0099208A1, Each of these publications is incorporated herein by reference. For example, Dressman et al., Proc. Natl. Acad. Sci. US A100:8817-8822(2003), International Publication No. 05 / 010145, or U.S. The present invention is described in Japanese Patent Publication No. 2005 / 0130173 or No. 2005 / 0064460. each of which is incorporated herein by reference in its entirety.

[0024] Other sequencing techniques that are applicable to the methods and systems described herein include pyrolysis. Sequencing, Nanopore Sequencing and Sequencing by Ligation Particularly useful representative pyrosequencing techniques and samples are described in U.S. Pat. No. 10891; No. 6258568, and No. 6274320 and Ronghi, Genome Research 11: 3-11 (2001), each of which is incorporated herein by reference. Representative nanopore techniques and samples that are similarly useful are described in detail in the article by Dr. eamer et al., Acc. Cem. Res. 35: 817-825 (2002); Li et al., Nat. Mater. 2: 611-6 15: (2003); Soni et al., Clin Chem. 53: 1996-2001 (2007); Healy et al., Nanomed. 2: 459-481 (2007) and Cockroft et al., J. am. Chem. Soc. 130: 818-820 and US No. 7,001,792, each of which is incorporated herein by reference. In particular, these methods utilize repeated steps of reagent delivery. The devices or methods described herein may be used to obtain desired profiles, such as those described in the above cited documents. Reservoirs, valves, fluid lines, and other components are required to introduce reagents and detect light according to a protocol. The fluid components are constructed using a control system for these components. Any of the various samples can be used to generate beads by emulsion PCR. a substrate with a zero-order wavelength; a substrate with an integrated CMOS detector; a substrate having a layer of biological nanopores, a solid-state substrate having a synthetic nanopore, and It may be used in systems with other substrates known in the art. The samples are described in the context of various sequencing techniques in the above references, as well as in U.S. Pat. Patent application publication numbers 2005 / 0042648, 2005 / 0079510, and 20 05 / 0130173, and WO 05 / 010145. each of which is incorporated herein by reference.

[0025] Various embodiments may be used to detect, for example, when present on or within a support structure. Exemplary labels that can be used include, but are not limited to, chromophores, luminophores, fluorophores ( Fluorophores), Optically Encoded Nanoparticles, Diffraction Grating Encoded Particles, Ru It can be detected based on electrochemiluminescence labels such as (bpy).sup.32+ or optical properties. Fluorophores that may be useful include, for example, europium. and fluorescent lanthanide complexes, including complexes of terbium, fluorescein, rhodamine, tetrahydrofuran, Methylrhodamine, eosin, erythrosine, coumarin, methyl-coumarin, pyrene, ma Lackite Green, Cy3, Cy5, Stilbene, Lucifer Yellow, Cascade Blue (registered trademark), Texas Red (registered trademark), Alexa dyes, phycoerythrin, bode and Haugland, Molecular Probes Handbook, (Eugene, Oreg.) 6th Edition; e Synthegen catalog (Houston, Tex.), Lakowicz, Principles of Fluorescence Spectr. oscopy, 2nd Ed., Plenum Press New York (1999)) or International Publication No. WO 98 / 59066 and US Pat. No. 6,399,623, each of which is incorporated herein by reference. In some embodiments, one label pair is excited by a first excitation wavelength. and another label pair can be excitable by a second excitation wavelength. can.

[0026] Embodiments include a method for detecting a sample containing a biological or chemical substance supported by an optical substrate. Although the present invention is illustrated with respect to the preparation of samples, it will be appreciated that other samples may be prepared using the embodiments described herein. Other exemplary samples include, but are not limited to, cells or tissue samples. biological samples such as those used in computer processors, and so on. Some example applications include microscopy, satellite scanners, high resolution copying, and fluorescence image collection. , Nucleic Acid Analysis and Sequencing, DNA Sequencing, Sequencing by Synthesis, microarray imaging, holographically encoded microparticle imaging, etc. There is. Summary of the Invention

[0027] According to embodiments described herein, a cartridge for use with a fluid analysis instrument is provided. The cartridge assembly includes a flow cell that receives the flow cell. The liquid storage device includes a liquid chamber and a well plate having a liquid well for receiving a desired amount of liquid. The well plate includes a housing that includes a valve station, a pump station, and a fluid analysis station. The pump assembly is mounted on the pump station and the fluid analysis stage. The rotary valve assembly controls the flow of fluid through a channel between the valve stage and the The rotary valve assembly is mounted on the well plate in the station. A rotor arranged to rotate about its center and selectively couple the well to the pumping station. The rotor shaft has a distal end that extends through the housing and is exposed. The rotor shaft includes a dual spline structure at a distal end thereof. The gear has first and second sets of splines. The first set of splines forms a drive interface. The first set of splines forms a position-coded interface, and the second set of splines forms a position-coded interface. The interface is used in the valve drive assembly to track the position of the rotor shaft. .

[0028] Optionally, the first set of splines extend around the outer surface of the distal end and adjacent splines thereof. The sides of the splines are spaced apart by a first predetermined spline spacing. The second set of splines corresponds to the spline pattern on the drive shaft of the valve drive assembly. The lines correspond to internal splines formed around the inside surface of a cavity located at the distal end. The internal splines are inclined so that their adjacent sides form a predetermined non-balanced angle with respect to each other. These adjacent sides blend together at the bottom to accommodate corresponding splines on the drive shaft of the drive assembly. A receiving recess may be formed.

[0029] Optionally, the rotor valve is attached to the proximal end of the rotor shaft by a coupling flange. The coupling flange may be provided to allow a predetermined amount of tilting between the rotor valve and the rotor shaft. The rotor valve may have one or more ribs disposed about the periphery of the proximal end of the rotor shaft. The rotor may include a rotor base having a coupling flange between the rib and the proximal end of the rotor shaft. The rotor valve may have a well plate contact surface having a central port and radial ports. The rotor valve may include a rotor valve extending radially outward from a central port to a radial port. The channel may include

[0030] Optionally, the central port is aligned with the axis of rotation of the rotor shaft and is The rotor valve may be aligned to coincide with the central feed port of the rotor valve. The rotary valve can be rotated to align the radial ports with the corresponding well ports. The well plate may include a well plate contact surface formed of an interface ring. The cartridge assembly may further include a rotary valve that is rotatable about the valve contact surface. The valve cap may include an internal cavity for receiving the valve cap. and one or more latch arms that secure the cap downwardly to the well of the well plate. A biasing element may be included in the internal cavity to provide a biasing force to the rotary valve. A sealed interface may be maintained between the port of the well plate and the port of the well plate.

[0031] Optionally, the pump assembly includes a plunger having a drive end and a bias surface on each end. The drive end and bias surface may be configured to provide a corresponding unidirectional drive in conjunction with the reciprocating motion of the plunger. exposed on the top and bottom of the housing so that force and bias forces can be applied to them. The plunger may be a drive arm and a plunger joined together in a U-shape by a bridge segment. The drive arm and the plunger arm may be integrally formed into a monolithic structure. The plunger arm may be housed within a support post located on the well plate. The plunger arm and plunger element are integrally molded from different materials. The plunger elements move in corresponding support posts to provide high and low pressure to the pump station. A pressure may be generated.

[0032] Optionally, the pump station may be functionally divided into a preparation section, a discharge section and a pumping section. and a channel section divided into a channel section and a channel section which are continuous with each other and allow fluid to pass in both directions. The pumping stations are located upstream and downstream of the working section. The pump assembly may include a working area sandwiched between a pair of pinch valves. The plunger may be aligned with the work area and adapted to reciprocate relative to the work area. The pump assembly includes a pushbutton that aligns with the pinch valve to introduce high and low pressure conditions. The push pins move alternately to open and close the pinch pins. The punch unit may be disposed within the housing and adjacent to the well. The punch unit can be moved to a punching position, where the punching elements are The cover of the well can be perforated.

[0033] Optionally, the housing may include a drilling section that provides equipment access to the upper end of the drill unit. The drilling unit may include a drilling access opening. The drilling unit may include a lower platform, a middle section, and The body may include a conical tubular shaped body having an upper flange, a lower platform or At least one of the upper flanges may include perforation elements distributed in a predetermined manner. The rotor unit may have a platform that fits over the rotor shaft. The form rotates the rotary valve assembly to align the piercing elements with the corresponding wells. An indexing mechanism that engages the engagement mechanism to position the punch unit in a predetermined rotational orientation. may include:

[0034] Optionally, the well plate is arranged in a predetermined pattern that corresponds to the rotating valve assembly. The well plate may include well transition ports arranged in a corresponding well. The well plate may include a well ejection port aligned with the corresponding well ejection port. and the well transition port. The plate may include a base having a top surface and a bottom surface, and a channel on at least one surface of the base. The base may include a side opening channel. The base may be bonded to the back layer. The well plate may be placed in an optical analysis station. The top surface of the well plate may include an optical interface window that is adapted to interface with the illumination elements of the instrument. The insertion limiting element may be provided around the optical interface window. These ribs may correspond to one or more ribs formed on the output element and the optical interface window. The Z tolerance between

[0035] According to embodiments described herein, a fluidic system including a cartridge assembly The cartridge assembly includes a housing that includes an illumination chamber and a well plate. The well plate is maintained within the housing and has a fluid channel for receiving a desired amount of liquid. The well plate includes a fluid analysis station aligned with the illumination chamber. The well plate is interfaced with an interface window located in the fluid analysis station. The flow cell cartridge has a frame that contains the analytical circuitry. The frame includes a flow cell window that aligns with the analytical circuit. The frame fluidically couples the active area within the analytical circuit. The housing includes a flow cell port that mates with the flow cell cartridge. The flow cell chamber includes a flow cell cartridge and a fluid analysis station. and aligning the flow cell windows and ports with the corresponding interface windows and ports. It has a.

[0036] Optionally, the flow cell chamber may include side rails and end stops; At least one of them is configured to insert the flow cell cartridge into the flow cell in a fully loaded position. The windows and ports are aligned with the corresponding interface windows and ports, respectively. The flow cell chamber may have end limits that are positioned at the reference points. The via may include a bias arm oriented to extend along at least one of the vias. The arm extends to the inside of the flow cell chamber and is connected to the flow cell cartridge. A lateral bias force may be applied to maintain the flow cell cartridge at a predetermined reference point. The bias arm is designed to fit into a notch on the side of the flow cell cartridge. The flow cell cartridge may include a latching element disposed thereon. The X reference point can be maintained with respect to an XYZ coordinate system (as described in the document).

[0037] Optionally, the flow cell cartridge may include a top and bottom frame. The top frame may include the flow cell window and port. The top frame may extend upwardly from the top frame by a predetermined height. Regarding the XYZ coordinate system The flow cell cartridge may include a gasket monolithically formed of an elastomeric material. The well plate may include a valve station, a pump station, and an interface channel, the interface channel providing a first fluid passage between the valve station and one of the interface ports and a second fluid passage between the pump station and one of the interface ports. The illumination chamber may be oriented to extend along an illumination axis that extends through the interface window, the flow cell window, and an active area in the analysis circuit. [Brief description of the drawings]

[0038] [Figure 1A] 1 illustrates a front top perspective view of a cartridge assembly formed in accordance with one embodiment described herein. [Figure 1B] FIG. 1B illustrates a bottom perspective view of the cartridge assembly of FIG. 1A according to one embodiment described herein. [Figure 1C] 1 illustrates a front perspective view of internal components within a cartridge assembly according to one embodiment described herein. [Figure 1D] 1 illustrates a top perspective view of a waste tray that is mounted below the well plate and forms a portion of the housing of a cartridge assembly according to an embodiment described herein. [Figure 1E] FIG. 1 illustrates a front perspective view of a portion of a cartridge assembly according to one embodiment described herein, with a flow cell cartridge aligned with a flow cell chamber. [Figure 1F] FIG. 2 shows a bottom view of a flow cell chamber and a flow cell cartridge inserted into the flow cell chamber according to one embodiment described herein. [Figure 2A]1 illustrates a perspective view of a rotary valve assembly formed in accordance with one embodiment described herein. [Figure 2B] 2 illustrates an enlarged perspective view of a distal end of a rotor shaft according to an embodiment described herein. [Figure 2C] 1 illustrates a cross-sectional view of a rotor valve assembly including a valve shaft according to an embodiment described herein. [Figure 2D] 1 illustrates a top perspective view of a rotor valve formed in accordance with embodiments described herein. [Figure 2E] 2 illustrates a bottom view of a rotor valve formed in accordance with one embodiment described herein. [Figure 2F] 1 illustrates a side perspective view of a rotor shaft and rotor valve with a rotor cap removed according to one embodiment described herein. [Figure 3A] 1 illustrates a bottom perspective view of a drill unit formed in accordance with one embodiment described herein. [Figure 3B] 1 illustrates a top view of a portion of a drilling machine unit when mounted on a rotary valve assembly according to one embodiment described herein. [Figure 3C] 1 illustrates a rotary valve assembly with the drill unit removed to better show the valve shaft according to one embodiment described herein. [Figure 4A] 1 illustrates a bottom view of a portion of the cartridge assembly to show the illumination chamber in greater detail, according to embodiments described herein. [Figure 4B] 1 shows a model cross-sectional side view of various structures provided in a fluid analysis station when a flow cell cartridge is inserted and an illumination element is inserted into the illumination chamber according to one embodiment described herein. [Figure 5A] FIG. 1 shows a top perspective view of a well plate formed in accordance with one embodiment described herein. [Figure 5B] 1 shows a flow channel on the rear side of the base of a well plate according to one embodiment described herein. [Figure 5C]1 shows a bottom view of a portion of a base of a well plate according to an embodiment described herein, providing a more detailed view of a fluid analysis station disposed on the rear side of the base. [Figure 5D] 5D shows a top view of the front / top portion of the base corresponding to FIG. 5C, providing a more detailed view of the fluid analysis station on top of the well plate according to embodiments described herein. [Figure 5E] 1 illustrates a close-up view of a portion of the bottom surface of the base adjacent the valve station according to embodiments described herein. [Figure 6A] FIG. 1 shows a top view of a pump station on a well plate according to one embodiment described herein. [Figure 6B] FIG. 2 illustrates a side view of a plunger in a pump according to one embodiment described herein. [Figure 6C] FIG. 1 illustrates an enlarged side view of a plunger element attached to a plunger arm according to one embodiment described herein. [Figure 6D] FIG. 2 illustrates a side view of a pump station to better illustrate pump operation according to one embodiment described herein. [Figure 6E] 1 illustrates an enlarged side perspective view of a portion of a plunger inserted into a support post according to one embodiment described herein. [Figure 6F] FIG. 1 illustrates a perspective view of a support shaft that houses a plunger arm according to one embodiment described herein. [Figure 7] 1 shows a block diagram of a portion of a fluidic device used in accordance with one embodiment described herein. [Figure 8] FIG. 1 is a schematic diagram of a system configured for biological or chemical analysis according to one embodiment described herein. [Figure 9A] FIG. 2 illustrates a top perspective view of a flow cell cartridge formed in accordance with one embodiment described herein. [Figure 9B] FIG. 2 illustrates a top perspective view of a flow cell cartridge formed in accordance with one embodiment described herein. [Figure 9C]FIG. 1 shows an enlarged view of a portion of the upper frame to better illustrate the optical fluidic (OF) interface of a flow cell cartridge formed in accordance with one embodiment described herein. [Figure 9D] 1 illustrates a top view of a portion of a printed circuit board provided within a flow cell cartridge formed in accordance with one embodiment described herein. [Figure 9E] 9D shows a bottom view of the printed circuit board of FIG. 9D formed in accordance with an embodiment described herein. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0039] Cartridge Assembly Overview FIG. 1A illustrates a cartridge assembly 1 formed in accordance with one embodiment described herein. 1 shows a top front perspective view of the cartridge assembly 100. As an example, the cartridge assembly 100 may be used in an SBS cartridge. The cartridge assembly 100 is inserted into a microfluidic device. Embodiments herein include a microfluidic system, an instrument, and a cartridge. Although described in connection with the ridge, the embodiment may also be used in "micro"fluidic systems, devices, etc. The housing may be mounted in a fluid system that is not considered a cartridge or the like. The cover 102 has an instrument contact surface 104. exposes internal components that engage with a number of equipment components, which are described in more detail below. In operation, cartridge assembly 100 is associated with performing a fluid operation. In close proximity to equipment that is physically, optically and electrically coupled to the cartridge assembly 100 The cartridge assembly 100 receives a flow cell in conjunction with the performance of fluidic operations. The device has a front surface 106 that includes a flow cell chamber 108 for receiving the liquid.

[0040] According to embodiments herein, the cartridge assembly 100 is made up of various subassemblies. For example, a rotating valve assembly 200 (described in more detail below in connection with FIGS. 2A-2D), A drilling unit 300 (described in more detail below in connection with FIGS. 3A-3D ), an illumination chamber 400 ( 4), and syringe pump assembly 500 (see FIGS. 6A-6C and (See below for more details on related matters.)

[0041] The cover 102 is a shaft cover that exposes the valve shaft within the rotary valve assembly 200. The cover 102 also includes drill access openings 122, which are Providing equipment access to the upper end of the drill unit 300 in conjunction with the operations described herein During operation, the drive shaft of the instrument rotates to govern the movement of the rotary valve assembly 200. The cover 102 is physically coupled to the valve shaft of the rotary valve assembly 200. 122, which are associated with the drilling operation of the well foil. Providing access for one or more drill shafts of equipment to the upper end of the drill unit 300 As an example, the plurality of drill access openings 122 may be arranged to accommodate the drill unit 300 at startup. To maintain surface motion, the drilling units 300 may be distributed along the top edge of the drilling unit 300. A sample well 124 is provided adjacent the front surface 106. The sample well 124 is Receive the sample volume of interest to be analyzed. Adjust (preheat) the temperature of the incoming sample as desired. To achieve this, a heating element 125 can be provided adjacent to the sample well 124. A pump access opening 123 is provided in the top surface 104 of the cover 102. The pump access opening 123 is A biasing element within the device urges engagement surface 542 into engagement with the plunger of pump assembly 500. For example, the biasing element may be a metal wave spring, an elastic spring, or a spring that provides a uniform force. It may be a separate structure.

[0042] FIG. 1B shows a bottom perspective view of the cartridge assembly 100 of FIG. 1A. 1, the flow cell cartridge 900 is inserted into the flow cell chamber 108. The cartridge assembly 100 has a bottom surface with a flow cell cartridge access area 112. 110, and an access area 112 is provided to access a portion of interest in the flow cell cartridge 900, e.g. 9, exposing an array of electrical contact pads 950 and an opening 944 for receiving a heating element. The bottom surface 110 also includes a pair of push pin holes 114 and a pump drive opening 116. The pin opening 114 exposes a push pin within the pump 500. As described herein The push pin engages a valve drive shaft within the device and acts in conjunction with the control of fluid flow. The pump drive opening 116 opens and closes the corresponding pinch valve in the valve shaft of the pump 500. 5, the proximal end 548 of the valve shaft 546 is exposed. engages a pump drive shaft within the device to provide pumping action associated with controlling fluid flow. The bottom surface 110 also includes an opening 118 that exposes a pierceable waste drain 120 for waste drainage. The port 120 is for draining used fluid from a waste container within the cartridge assembly 100. Used for.

[0043] FIG. 1C illustrates an internal compartment within a cartridge assembly 100 according to one embodiment described herein. As shown in FIG. 1C, a front perspective view of the cartridge assembly 100 is shown. The valve is rotatably mounted on a well plate 150 in a valve operation station. The syringe pump assembly 500 is attached to the pump station. The well plate 150 is attached to a base 152 (e.g., The base 152 includes a base plate 152a and a base 152b. The reagent wells 154, 156 are connected to a rotary valve The reagent wells are provided at various locations at least partially surrounding the assembly 200. If necessary, the rotating valve assembly 200 can be rotated to rotate the sample wells 154, 156 (commonly referred to as fluid wells) are selectively coupled to a fluid analysis station 170 .

[0044] The reagent wells 154, 156 have different cross sections to receive desired amounts of the corresponding reagents. The wells 152 are formed to have different heights above the base 152 and different well volumes. Optionally, one or more of wells 154, 156 may be configured according to the embodiments described herein. Wells 154, 156 may be used as solution wells if desired. The well 154 includes a fill end 158, 160 that is open to receive the body. Once filled, the fill ends 158, 160 are covered with a foil or other sealing cover. The air gap is then filled with air to form an airtight volume within each well 154, 156. The valves 154, 156 include one or more outlets at their bottoms. Under the control of 200 and pump assembly 500, the cover is perforated to allow air to enter one or more Once in the well volume, the liquid is then directed through an outlet to a fluid analysis station 170. It is allowed to flow freely (eg, by gravity or under pressure).

[0045] FIG. 1D shows the cartridge assembly 100 mounted under the well plate 150. 1 shows a top perspective view of a waste tray 130 forming a part of the housing. The plate 150 includes a waste collection volume 131 that extends over the lower area of ​​a relatively large portion of the plate 150. By way of example, the waste tray 130 may include a rotating valve assembly 200 and a small number of wells 54, 156. The waste tray 130 extends along its periphery and is (e.g. For example, the well plate 150 includes a ridge 132 that is sealed to a mating surface (on the bottom surface of the well plate 150). The well 132 includes a vent hole 133 at its corner that communicates with a through opening in the well plate 150. The vent 133 allows air to escape from the volume 131 as the waste liquid enters the volume 131. The ventilation hole 133 can be opened at least partially even if the device is tilted slightly during operation. The holes are distributed so that one can always be used as an air intake. Even if the liquid splashes onto the surface of the hole 133, it will not leak, so the size of the waste liquid tray 130 can be limited. The ventilation hole 133 is made of expanded polypropylene, polyethylene, or polytetrafluoro. It may be made of a porous material such as ethylene.

[0046] The waste tray 130 also includes a funnel 134 and a drain tube 135. The funnel 134 is connected to the opening of the tube 135. The bottom end of the tube 135 is first covered with a cover. To empty the fluid tray 130, the cover 136 is pierced and the cartridge assembly 1 is removed. 00 (including the waste tray 130) can be tilted to place the funnel 134 in its lowest position. The waste liquid passes through funnel 134, over ledge 136 and out tube 135.

[0047] Flow Cell Chamber FIG. 1E illustrates a portion of the cartridge assembly 100 and the flow cell chamber 108. A front perspective view of the aligned flow cell cartridge 900 is shown. The flow cell chamber 108 is The key mechanism 109 is formed as a groove, and the flow cell chamber 10 The key mechanism 109 is provided on the bottom surface of the flow cell cartridge 900. 9. The flow cell cartridge 900 is loaded in the correct orientation and with the corresponding key features on the bottom of the cartridge. The front end is shaped and sized to receive a structural part (e.g., standoff 914 in FIG. 9C). The cell chamber 108 includes side rails 413 and top and bottom walls 451 and 453. Cartridge 900 is inserted in a loading direction 900A.

[0048] FIG. 1F illustrates a flow cell chamber 108 and an insert therein, according to one embodiment described herein. A bottom view of the inserted flow cell cartridge 900 is shown. At 1F, it is inserted into the flow cell chamber 108 to the fully loaded position. As described in more detail in connection with Figures 9A-9E, a flow cell cartridge The mount 900 includes a loading end 908 and a side edge 912. The loading end 908 includes a reference post 923. At least one of the side edges 912 includes one or more reference posts 925. The side edge 912 includes a notch 927. The bottom surface of the flow cell cartridge 900 is fitted with a heat diffuser 9 57 and has openings exposing contact pads 950.

[0049] The flow cell chamber 180 is connected to each other along the top and bottom surfaces and along opposing sides of the chamber 108. The chamber 108 includes side rails 413 extending parallel to the wall of the chamber 108. End stops 417 are provided at the top of the chamber 108. The top and bottom surfaces, side rails 413, and end stops 417 are The row cell cartridge 900 is aligned with a predetermined reference point ( For example, the reference points called the X reference point, the Y reference point, and the Z reference point are End stops 417 are provided at desired locations along the end stops 417. The end limiter 414 is provided at the loading end 908. One of the side rails 413 is aligned with the reference post 923 inside the flow cell chamber 108. The lateral limiter 420 extends toward the lateral reference portion. The opposite side rail 413 extends along the side rail 413. bias arm 42 oriented to provide a lateral bias force in the direction of arrow 1E 2. Bias arm 422 includes latch element 424 at its distal end. Latch element 4 24 is shaped to fit into notch 927 in side edge 912 .

[0050] During the loading operation, the loading end 908 is mounted in the flow cell chamber 108 with a reference post 923 . The limit mechanism in the flow cell chamber 108 that defines the limit of movement in the filling direction 9A is firmly attached to the limit mechanism. As the flow cell cartridge 900 is inserted, the vias Along the side edge 912 where the arm 422 includes a notch 927, the latch element 424 is 27. Bias arm 422 applies a lateral force in the direction of arrow IE. The flow cell cartridge 900 is then moved in the lateral direction (corresponding to the Y-axis) so that the lateral reference post 923 The lateral boundaries of the flow cell chamber 108 are The bias arm defines the limit of movement in the lateral (Y) direction. The latch element 424 in the notch 927 is held at the desired Y position (corresponding to the Y reference point). This position maintains the flow cell cartridge 900 at the desired X position (X reference point).

[0051] The flow cell chamber 108 allows for snap-in placement of the flow cell cartridge 900 The flow cell cartridge 900 is inserted into and removed from the cartridge assembly 100. By allowing for the insertion and removal of a flow cell, the embodiments described herein This allows the cartridges to be managed and delivered separately from the reagents and samples. By separating the cell cartridge 900 from the reagents, the embodiments described herein Additionally, the embodiments described herein enable a workflow for the production of flow cells. Cartridges can be mixed with a variety of reagent combinations, reagent volumes, and flow cell cartridge sizes. For example, one protocol may use large amounts of a given reagent. While other protocols use many small amounts of different reagents, variations in the number and amounts of reagents are possible. Although various criteria can be met with different cartridge assemblies, the cartridges described above are Any of the ridge assemblies can use the same flow cell cartridge. In an embodiment, the same type of circuitry can be used for different protocols that have different requirements on the analysis circuitry. For example, one protocol is a large Another protocol may use an analysis circuit that has a small optical footprint. In addition, some processors may use analysis circuits that have a small optical footprint. Tokol is a analytic circuit that has more complex electronic circuits and interconnections compared to other analytic circuits. Any of the above mentioned analysis circuits may be housed in the same cartridge assembly. The flow cell cartridge may be embodied in a common overall envelope. do.

[0052] The embodiments described herein provide a small height ( For example, provide an interface with a minimized height.

[0053] Drilling Machine Unit The drilling unit 300 is mounted within the housing and is located adjacent to the wells 154, 156. The drilling unit 300 is moved to a drilling position where the drilling elements are aligned with the corresponding webs. The foil or cover of the foils 154, 156 is punched. The well 300 is mounted in the rotary valve assembly 200 and is rotated by the instrument during operation. , 156.

[0054] FIG. 3A illustrates a bottom bevel of a drill unit 300 formed in accordance with one embodiment described herein. The drill unit 300 is partially cut away to better show the overall structure. The drill unit 300 includes a lower platform 302 and a middle section 308. The platform includes a body 306 shaped like a cone tube having a top flange 310. The arm 302, the portion 308 and the flange 310 are integrally formed. 02 includes perforation elements 312 distributed in a predetermined manner around the periphery of the platform 302 . In the embodiment of Figure 3A, the piercing elements 312 are arranged in a circular pattern. 310 also has a perforation element 314 provided on its underside, which protrudes in the same direction as the perforation element 312. The perforation elements 314 are arranged in a predetermined manner around the periphery of the upper flange 310, for example in a circular pattern. It is distributed in

[0055] In operation, the drill unit 300 is driven by the drill actuator assembly of the instrument. For example, referring to FIG. 1A, the device may include a cover 102 for covering one or more drill shafts. The drill shaft can extend through the drill access port 122. 18, which pushes down the punching unit 300 to cause the punching elements 312, 314 to face each other. The drill shaft is driven to penetrate the foil / cover of the corresponding well 154, 156. The holes are distributed to provide an even drilling force to the punch unit 300.

[0056] According to at least one embodiment, the piercing elements 312, 314 are Formed in an X-shaped cross section to facilitate drilling and provide ventilation through the foil / cover The X-shaped cross section allows the piercing elements 312, 314 to penetrate the foil / cover while still being compliant. This allows air to flow into the wells.

[0057] In the embodiment of FIG. 3A, the majority of piercing elements 312, 314 have a substantially common length. However, if desired, each of the piercing elements 312, 314 may be, for example, piercing element 314A. As shown in FIG. 1C and FIG. 3A, , the piercing elements 312,314 are positioned to align with corresponding wells 154,156. In the embodiment of FIG. 1C and FIG. 3A, when the piercing element 300 is actuated, the corresponding well 5 In order to simultaneously pierce each of the 14,516, the piercing elements 312,314 have a generally common length. Optionally, the drill unit 300 may be (for example) a drill actuator assembly. Thus, the system operates as a multi-stage drilling system, with only a portion of the drilling elements 312, 314 being first During the drilling operation, corresponding wells 154, 156 are drilled and different Only a portion of the wells 154, 156 may be drilled during the second drilling operation. For example, piercing element 312 may be longer than piercing element 314 such that piercing element 412 is the first piercing element. During a drilling operation, the corresponding foil is pierced, and the piercing element 314 pierces the corresponding foil during a second drilling operation. The file may be punched.

[0058] The lower platform 302 includes an inner rim 326 formed around the periphery of the opening 304 . The rim 326 includes a number of indexing mechanisms disposed around the periphery of the opening 304. The rotary mechanism 322 rotates the drilling machine unit 300 relative to the rotor shaft 202 at a predetermined speed. to orient and align the piercing elements 312, 314 with the wells 154, 156. The index mechanism 322 engages with the engagement mechanism of the rotary valve assembly 200. The rim 326 includes one or more notches 324 disposed about the periphery of the body 306. The notch 324 projects slightly upward toward the upper flange 310. The notches 324 are distributed in a predetermined pattern around the circumference of the substrate 4 (as will be described in more detail below). 2) align with ribs or teeth provided on the rotary valve assembly 200. In the embodiment, the notches 324 are relatively evenly spaced around the circumference of the opening 304. 2. Alternatively, more or fewer notches 324 may be used, evenly or unevenly spaced in alternative positions. If desired, an indexing mechanism other than notch 324 may be used.

[0059] The rim 326 may include one or more ribs 326 extending downwardly within the aperture 304 in a common direction with the piercing element 312. The standoffs 328 are disposed around the periphery of the base extension 216. The notch 324 engages with the ledge 216A that extends around the circumference of the rotary valve assembly 2. 00, the punch unit 300 will be aligned such that the standoff 328 is aligned with the ledge 2 16A. Standoff 328 remains on ledge 216A. 3 to maintain the drill unit 300 in a vertically non-drilling / ready position. The punch unit 300 is then pushed downward (in the direction of arrow 318) by the punch shaft. In response, the standoffs 318 bend outward and rest on the ledge 216A, causing the drill unit to Sliding knit 300 downward in drilling direction 318 onto rotor cap 210. can be done.

[0060] FIG. 3B illustrates the drill unit 300 when attached to the rotary valve assembly 200. As described herein, the rotary valve assembly 200 is The valve cap 210 is attached to the rotor shaft 202. The bubble cap 210 is made up of multiple ribs distributed around the central rim of the bubble cap 210. The teeth 212 align with and mate with notches 324 in the punch unit 300. The drilling machine unit 300 is rotated to a predetermined rotation angle relative to the rotary valve assembly 200. Although not shown, the drilling machine unit 300 is attached to the rotary valve assembly 200. To maintain the rotor shaft 202 in a mounted position along a rotational axis extending along the central axis of the rotor shaft 202 Then, the latch 328 (FIG. 3A) is securely coupled to the latch mechanism of the valve cap 210. do.

[0061] FIG. 3C shows the drill unit 300 removed to provide a better view of the rotor shaft 202. The rotary valve assembly 200 is shown in FIG. 0. The rotor shaft 202 has a proximal end (not visible in FIG. 3C) and a distal end 2 04. The valve cap 210 is attached to the distal end of the rotor shaft 202 as shown in FIG. 204 in a mounted position. The cap base portion 214 includes a substantially circular array of wells 156 arranged adjacent to one another. The cap base portion 214 has an enlarged diameter sized to fit within the group. A cap base 214 extends upwardly from the cap base 214 along the length of the motor shaft 202. 3C. However, the cap extension 216 and the cap base portion 214 have a diameter smaller than that of the cap base portion 214. It will be appreciated that other dimensions may be used for the cap base portion 214. 216 is a radial (with respect to the axis of rotation 220) axially extending portion formed around the cap extension 216. 2 includes outwardly projecting teeth 212.

[0062] The cap base portion 214 includes one or more cap members extending radially outwardly from the cap base portion 214. The latch arm 226 includes an upper latch arm 226. The latch arm 226 is L-shaped and The legs of the latch arms 226 are sized to fit between adjacent wells 156 and The outer portion or foot of the well 156 is bent around the outside surface of the well 156 and fits securely thereon. The corresponding well 156 includes a detent 158 ​​on its outer wall. The latch arm 226 is secured to the rotor shaft 202 when the valve cap 210 is inserted onto the rotor shaft 202. When it is seated, it snaps in and is held securely under detents 158.

[0063] Rotary Valve Assembly The operation of the rotary valve assembly 200 will now be described in conjunction with Figures 2A-2F.

[0064] FIG. 2A illustrates a rotary valve assembly 20 formed in accordance with one embodiment described herein. FIG. 2A shows a perspective view of the valve cap 202 provided to cover the rotor shaft 202. 10. The rotor shaft 202 rotates within the valve cap 210, The cap 210 holds the rotor shaft 202 in place relative to the well plate 150. The valve cap 210 has a number of evenly distributed cap base portions 214. The distal end 204 of the rotor shaft 202 includes a cap extension 226. 16. The distal end 214 is formed of a plurality of ribs 216 distributed around the rotor shaft 202. The distal end 204 also includes a cavity 228, the periphery of which is formed with a spline 230. The rotor shaft 202 includes internal and external splines 2 Dual splines having 32,230 (also referred to as the first and second sets of splines) The spline structure includes a mechanism for engaging the cartridge assembly during fluid operations. The valve drive assembly is then fitted with a corresponding splined structure on the drive shaft of the valve drive assembly within the vessel. The dual spline structure of the external splines 232 and 230 is designed to connect the drive shaft of the equipment to the load. Position controller for accurate tracking of the drive interface and rotational relationship between the drive shaft 202 and the It provides a code-driven interface.

[0065] The valve cap 210 is attached to the bottom of the valve cap 210 proximal to the rotor shaft 202. 2 is shown partially see-through to show the rotor valve 234 mounted around the end. The rotor valve 234 is fixed to the rotor shaft 202. 2. The rotor valve 234 rotates within (relative to) the cap base portion 214. 3, the cap base portion 214 rotates in a direction perpendicular to the axis of the cap 214. It remains stationary by latch arms 226 fixed around its periphery. The inner diameter of the rotor shaft 202 corresponds to the outer diameter of the rotor shaft 202, allowing for close tolerances therebetween. If cap extension 216 provides sufficient structural and rotational support, cap extension 216 may be 16 has a variable length 217, whereby the axis of rotation of the rotor shaft 202 is The rotor shaft 2 is maintained in a fixed position relative to the support plate 150. The axis of rotation of 02 corresponds to the central port in the well plate through which fluid moves. As described herein, the desired one of the wells 154, 156 may be aligned with the rotor shaft 20. The valve drive assembly of the instrument is adapted to fluidly couple to the lower center port of the rotor. This rotates the rotor shaft 230 which in turn rotates the rotor valve 234 .

[0066] FIG. 2B shows an enlarged perspective view of the distal end 204 of the rotor shaft 202. Lines 232 and 230 have different spline configurations. The external spline 230 is the drive inlet. The first / outer spline corresponds to the first set of splines that make up the interface. The internal spline 23 engages with a corresponding spline on the drive shaft of the lube drive assembly. 2 corresponds to the second set of splines that make up the position-coded interface and Assembly provides sufficient clearance between the valve drive assembly drive shaft and rotor shaft 202. The external spring is used to keep the interconnection mated (and closely tracked) with the external spring. The lines 230 have spline sides 233 that extend generally parallel to one another. The splines 230 are spaced apart by two adjacent spline sides 231. 33 are oriented to extend parallel to one another. The spline spacing 231 is Corresponds to the spline pattern of the drive shaft of the assembly. Spline spacing 231 are slightly larger than the corresponding splines from the drive shaft assembly for ease of engagement. By giving the spline spacing 231 larger than the incoming splines, This allows for a small amount of slack to be introduced, which allows for a limited amount of relative movement between the rotor shaft and the drive shaft. Therefore, the splines of the drive shaft are Instead, the internal spline 232 provides a position-coded interface. The interface comprises a drive assembly interface as described herein. When combined with a separate location coding / tracking element, it can be used to provide location coding information. The position-coded interface is used to interface the drive spline with the external spline 230. The valve drive assembly is designed to closely and accurately track the rotor shaft position regardless of the input. The internal splines 232 are utilized such that adjacent sides have a predetermined non-planar surface relative to one another. It has side surfaces 235 that flare out in a V-shape to form a side angle 237 (e.g., 30 degrees). Surface 235 blends with the bottom surface of internal spline 232 to form a drive shaft for the valve drive assembly. The splines 232 form V-shaped recesses that receive corresponding splines on the drive shaft. The splines 232 are fully engaged with the corresponding splines on the shaft to cooperate without backlash. It also allows the shaft to operate in a somewhat "tilted" position relative to the rotor shaft 202. The splines 230, 232 and the distal edge of the distal end are configured with a bevel edge to facilitate alignment of the drive shaft. This allows for easy shaft alignment and allows the drive shaft to be mounted without the need for spline alignment. This can prevent the ball from simply hitting the rotor shaft 202.

[0067] The dual spline design of Figure 2B provides a relatively "loose" fit to the splines of the valve drive assembly. The rotor shaft 2 is driven by an external spline 230 that is tightly engaged with the rotor shaft 2. Internal splines relatively "closely" coupled to a position encoder that monitors the rotational position of the 02 Use 232.

[0068] FIG. 2C illustrates a rotor shaft 202, a valve cap 210, and a rotor valve 234. FIG. 2B shows a cross-sectional side view of a rotary valve assembly 200 including a rotor shaft 202. The rotor shaft 202 is elongated and has an axis of rotation 220 at its center. The valve cap 210 holds the valve in place so that it can rotate freely. The cross-sectional envelope of the cap 210 is shown, with the cap base portion 214 being the cap extension portion 21 The cap extension 216 has a diameter greater than that of the rotor shaft 202. The cap extension 216 includes an internal passage 219 having a matching inner diameter. The internal passage 219 of the cap extension 216 The rotor shaft 202 is held in a predetermined orientation, and the rotation axis 220 is aligned with the desired position on the well plate. It is centered on a point (eg, the central feed port).

[0069] FIG. 2D illustrates a top view of a rotor valve 234 formed in accordance with one embodiment described herein. The rotor valve 234 has a rotor having an upper surface and a well plate contact surface 238. The rotor base 240 is made of polypropylene or any other suitable material having the desired properties. The rotor base 240 may be injection molded from another material. The fluid channel 246 is aligned with a central port 248 at a central point of the rotor base 240 . The fluid channels 246 are directed radially outward from the periphery of the rotor base 240. The central port 248 and the radial port 250 extend to a point and terminate at a radial port 250. The central port 248 passes through the rotor base 240 and communicates with the well contact surface 238. The rotor shaft 202 is aligned with the axis of rotation 220 of the rotor shaft 202, and the well The rotor valve 234 may be aligned with a central feed port with a flow rate of 150. The radial ports 250 are connected to corresponding wells in conjunction with drawing up a reagent or sample of interest from the wells. 252 about the axis of rotation 220 to align with the transition port 162 It is rotated.

[0070] The upper surface of the rotor base 240 includes a recess 261 that surrounds the fluid channel 246. 261 is configured to receive a channel cover 258 that covers the open surface of the fluid channel 246 The channel cover 258 extends the entire length of the fluid channel 246 and covers the fluid channel 246. In this embodiment, the open-faced fluid channel 246 and the The fur cover 258 is used to provide an easy and reliable manufacturing process. Accordingly, an alternative structure may be used to provide a fluid channel while removing the channel cover 258. For example, fluid channels can be formed within the monolithic structure of the rotor base 240. 258. This eliminates the need for a channel cover 258.

[0071] The upper surface of the rotor base portion 240 is formed with a peripheral rib 24 extending upward from the rotary valve portion 240. 2 and internal ribs 256. The well plate contact surface 238 has peripheral and internal ribs 242. , 256. A biasing element 253 (e.g., a wave spring or other structure) A biasing element is disposed within the internal cavity 213 and provides a biasing force to the rotor valve 234. 253 rests on rotor base 240 around internal rib 256. 53 applies an expansion force to the rotor base 240 and the valve cap 210 to expand the rotor valve 23 Maintain a sealed interface between ports 248, 250 of the well 4 and the ports of the well plate 150 .

[0072] FIG. 2E shows a bottom view of rotor base 240. Well plate contact surface 238 is The interface ring 260 is formed by the rotor base portion and the interface pad 262. 2C, interface pads 262 in interface ring 260 extend around the periphery of interface ring 240. 2. The rotor base 240 is supported by a small standoff that keeps the rotor base 240 away from the well plate 150. In one embodiment, the interface ring 260 may be formed with a smooth flat underside. In this embodiment, the interface ring 260 is in contact with the well plate 150. A pattern is formed on the outer surface of the interface ring 260 to reduce its area. For example, the pattern may be formed on the interface ring 260 (e.g., in a chain pattern). For example, the casing may comprise a group of interconnected circular or O-ring shaped parts. FIG. 2E shows an alternative configuration of the surface of interface ring 260. In detail FIG. 2E, interface ring 260 A has a series of circular raised rings / portions 261A surrounding a recess 262A. The pattern of FIG. 2E may resemble a chain or row of eight adjacent rings, but may be different from that of another putter. When not in use, the interface ring 260A is recessed such that the recess 262A is flush with the well. The rate port can be rotated into alignment with the rate port to avoid creep within the port structure. do.

[0073] The rotor base 240, interface ring 260 and interface pad 262 are multi-shot (e.g. The rotor base can be formed by a single-shot (e.g., two-shot) molding process. The interface ring 260 and the interface pad 262 are formed of one type of material. For example, the interface ring 260 and the interface pad 262 can be made of a thermoplastic elastomer ( The radial ports 250 may be formed of an interface ring. 260. An interface pad 262 is formed around the periphery of the central port 248. The feed port 248 is positioned to align with the center feed port 161 of the well plate 150. However, the radial ports 250 are arranged to align with different well transition ports 162. The central interface pad 262 and the interface ring 260 are rotated in a common injection molding operation. It is formed by injecting thermoplastic elastomer through one or two gates. The facing ports 250 are arranged along an arc (relative to the central port 248) around the periphery of the interface ring 260. The elliptical radial port 250 may be formed as an ellipse having an elongated dimension. Provides a predetermined amount of tolerance when aligning with the well port.

[0074] FIG. 2F is a side perspective view of rotor shaft 202 and rotor valve 234 (rotor 210 is FIG. 2F shows rotor shaft 202 extending along axis of rotation 220. The proximal end 203 of the rotor shaft 202 is connected to the rotor valve through a load coupling interface 239. The load coupling interface 239 is secured to the coupling flange 241 therein. The coupling flange 241 is formed with an internal rib 256 that holds the rotor shaft 202 in place. The rotor shaft 202 includes a sidewall 243 extending along a desired section of the rotor shaft 202. The coupling includes a base section 245 and an upper section 247 extending at least partially along the coupling. Flange 241 decouples rotor shaft 202 from rotor valve 234 (e.g., In addition, the connecting flange 241 allows the rotor shaft to be Side loads on the wing 202 can be decoupled from the rotor valve 234. For example, The side loads are observed in various radial directions as shown by arrows 2F, and the rotor This may cause a slight deflection of the shaft 202. The coupling flange 241 is connected to the rotor shaft 202. A predetermined amount of tilting is permitted between the rotor and the rotary valve, for example, in the direction of the arrow 2F. The valve 234 is maintained in a relatively constant orientation relative to the surface of the well plate. Alternatively, rotor valve 234 may be maintained within a predetermined plane designated by coordinates XY.

[0075] Returning to FIGS. 2A, 2B, and 3C, the rotary valve assembly 200 includes various mechanical components. The latch arm 226 holds the valve carrier in place over the well plate. The tip 210 is fixed at a predetermined XY position on the well plate 150 relative to the well 156. (FIG. 3C). An indentation on the wall of well 156 (FIG. 3C) holds latch arm 226 and bubble cap 228 in place. The cap extension 216 holds the rotor shaft 202 at a predetermined X. Y position, orientation, and rotation about axis of rotation 220. Internal rib 256 A bias element 253 disposed within the cap base portion 214 (FIG. 2B) biases the cap base portion 214 to the internal cavity 21. 3. The internal shelf 221 is disposed in the downward direction of the bias element 253. The rotor base 240, the interface ring, and the rotor base 240 maintain the force while allowing rotational motion. Firmly press and hold the pad 260 and the central interface pad 260 against the surface of the well plate 250. Hold.

[0076] Illumination Chamber FIG. 4A illustrates the cartridge assembly 400 in more detail. 1 shows a bottom view of a portion of 100. The illumination chamber 400 is adapted to receive the illumination elements of the device. For example, the lighting elements are arranged in the lighting chamber 40 according to predetermined XYZ coordinates. 0. As will be described later, LED lighting elements are installed within the illumination chamber 400 (e.g. For example, LED lighting elements are inserted into the dock (inside the The position is determined by a position limiting mechanism within the illumination chamber 400.

[0077] 1A, 5C and 5D, the illumination chamber 400 has a circular peripheral wall 4 on one side. 06 is formed on the opposite side and position limiter 408 (FIG. 5D) is formed on the opposite side. are provided at selected points around the periphery of the fluid analysis station 170. The position limiters 408 are The illumination element is provided, for example, in a well plate 150 by engaging with an engagement mechanism on the peripheral outer wall of the device. The optical interface window 410 is then positioned at a known desired position in the XY directions relative to the optical interface window 410 . In this embodiment, the XY direction extends in a plane approximately parallel to the surface of the optical interface window 410. In addition, one or more ribs 412 are provided on the well plate 150 to accommodate optical interfaces. The lighting element is disposed around the periphery of the interface window 410. When the lighting element is inserted in the Z direction, the ribs 412 (provides a reference point for the lighting element). The Z direction of the lighting element (towards or away from the optical interface window 410) is abutted against the front surface of the Optionally, additional or more controllable light sources may be provided in conjunction with controlling the position of the lighting elements. Fewer limiters 408 and ribs 412 may be used. XYZ directions may be different if desired. It may also be aimed at a shape.

[0078] As described in detail herein, the channel cover includes an optical interface window 410 and In one embodiment, the fluid channel is formed over the well. The plate 150 is formed with an opening on the top surface thereof, and a channel above the fluid channel. The cover may be laser bonded (or otherwise) attached.

[0079] FIG. 4B illustrates a flow cell cartridge 900 inserted according to one embodiment described herein. When the illumination element is inserted into the illumination chamber, the illumination element is presented at the fluid analysis station 170. 4B shows a model cross-sectional side view of various structures that may be provided. In FIG. The flow cell cartridge 90 is illuminated in the operating position above the flow cell plate 150. 0 is inserted into the flow cell chamber 108. The structure includes a window 410, a rib 412, ports 180, 182 and a channel cover 416 and 4 18. The structure of the flow cell cartridge 900 seen in FIG. 4, flow cell window 928, port 934, and analysis circuit 958. Analysis circuit 958 includes The illumination chamber 400 includes an active area 962 and an active area port 964. Through the flow cell window 410, the flow cell window 928, the transparent layer 429 and the active area 962 in the analysis circuit. The light source 4 is oriented to extend along an illumination axis 4B.

[0080] The illumination element 450 is inserted into the illumination chamber 40 until it abuts the rib 412 of the well plate 150. 0. The rib 412 defines a Z datum point for the lighting element 450. The light emitted from the lighting element 450 is reflected by the window 410 at a predetermined distance (minimum distance). 10, passing through the flow cell window 928 and the transparent layer 929 to the upper surface of the analysis circuit 958. Ports 180 and 182 in well plate 150 form channels under covers 416 and 418. The ports 180 and 182 control the inlet and outlet of the fluid passing through the flow cell cartridge 9. 00 upper frame 904 and port 934 is In one flow direction, the fluid passes through the channel cover. Enter the channel corresponding to 418 and move down ports 180, 194 and 964 The fluid can pass through the ports 964, 934 and 182 to the channel cover 41. 9. The ion beam moves across the active area 962 until it is discharged into the channel corresponding to 6. , the flow direction may be reversed.

[0081] Optionally, electrodes may be placed adjacent to one or more of ports 180, 182, 934, or 964. Further, the analysis circuit may be arranged to generate a potential by the fluid in the active region. It can also function as an opposing potential.

[0082] Well Plates Next, the well plate 150 and the network of fluid channels in the well plate 150 are The well plate 150 includes a thin channel In one example, the well plate 150 may have side openings formed on one or both sides. The mouth may be formed of a base layer having a network of fluid channels. To close the side openings, the top and / or bottom surfaces of the base layer are bonded to a corresponding back layer (e.g. , plastic film) is sealed. For example, only the bottom surface of the base layer has a side opening. In the case where the channel is included, the back layer is provided only on the bottom surface. If only the top surface contains side-opening channels, the back layer need only be provided on the top surface. If the top and bottom surfaces of the backing layers include side openings, the front and bottom backing layers are It may be provided on the top and bottom surfaces of the layer.

[0083] Optionally, one or both of the base layer and the back layer may be made of polypropylene film, thermoplastic The base layer and / or the back layer may be made of a thermoplastic elastomer, a vulcanized thermoplastic elastomer, etc. The layers may be bonded together by various methods, such as laser bonding. The base layer is provided with a means for interconnecting channels on the top and bottom surfaces of the base layer. It includes a network of ports that pass through it.

[0084] All or part of the base layer may be formed from carbon loaded black plastic or similar material. The addition of carbon makes it easier to perform laser bonding with the joining structure and reduces the size of the joining area. Make the surface at least partially opaque by using black plastic or other opaque material. Thus, the well plate 150 provides a desired amount of resistance to light exposure and unwanted fluorescence. Reducing autofluorescence of the flow cell cartridge by preventing transmission or reflection The well plate 150 improves the system by preventing unwanted light transmission or reflection. It also reduces optical noise in the system.

[0085] FIG. 5A shows a positive electrode of a well plate 150 formed in accordance with one embodiment described herein. FIG. 5B shows a front perspective view of one implementation of a network of side-opening channels described herein. The bottom surface of the base 152 of the well plate 150 is shown to better illustrate the configuration. A back layer is provided on the bottom surface of the base 152 to close the side opening channels. The well plate 150 can include a valve station 164, a pump station 168 and a fluid analysis station 170. Sample inlet channel 172D includes sample inlet 1 24 to the sample transition port 162D. The station 164 includes a plurality of wells 154, 156 disposed around the periphery of the station 164. Some of the valves are arranged in a circular pattern around the valve station 164. A circular flange 166 is formed on the base 152 within the cavity 164 (which extends upwardly). The flange 166 has an inner circular shape that matches the shape of the rotor base 240. The flange 166 and the portion of the well plate within the flange 166 are attached to the rotating valve assembly 200. The inner surface of the flange 166 is generally flush with the outer periphery of the rotor base portion 240. Optionally, the flange 166 may be fitted to the rotating valve portion 240 and the well plate. This can also facilitate maintaining a sealed relationship between the housing 150 and the outlet 150.

[0086] An array of well transition ports 162 is disposed on the base 1 within the inner region of the flange 166. 52. The well transition port 162 is provided at the rotary valve assembly 200. The pattern is formed in a predetermined shape corresponding to the movement pattern and range of motion, for example having a predetermined radius. For example, the well transition port 162 is formed along a circular arc extending along the fluid channel 2. The central feed port may be formed along a circle having a radius equal to the length of the central feed port 46 (FIG. 2C). The well 160 is defined by the center of the flange 166 and the well transition port 162. The central feed port 161 is located at the center of the circle that is the center of the rotation axis 2 of the rotor shaft 202. 20, and the rotary shaft 220 is formed through the rotor valve 234. It also coincides with the central port 248.

[0087] The pump station 168 includes first and second support poles extending upwardly from the base 152. The support posts 502, 504 support the drive of the pump assembly 500. The support posts 502, 504 receive the drive shaft and the syringe arm. The movement of the syringe arm is guided along a predetermined reciprocating linear path to deliver the fluid to the cartridge assembly. The fluid analysis station 170 delivers the fluid to the flow cell and Remove the fluid from the row cell.

[0088] FIG. 5B shows a side opening flow channel provided on the bottom surface of the base 152 of the well plate 150. The flow channels 172 are connected to the pump station 168, It extends through the valve station 164 and the fluid analysis station 170. Alternatively, the flow channel 172 may pass through additional stations. The holes 172 may be formed in a variety of patterns and have a variety of lengths and diameters.

[0089] FIG. 5E shows an enlarged partial view of the bottom surface 153 of the base 152 near the valve station 164. 1. Valve station 164 corresponds to the path along which rotary valve assembly 200 travels. Well transition ports arranged in a predetermined pattern (e.g., a circular pattern) to 162. The well plate 150 further includes a well ejection port 163. Ports 163 extend through base 152 and into the base within corresponding wells (not visible in FIG. 5A). Each well discharge port 163 is connected to a well discharge channel 165. The well plate 150 is connected to the corresponding well transition port 162 through the well transition port 162. Depending on the number and location of the wells 154, 156, the well may contain multiple well drainage channels 165. Well discharge channels can be formed in various shapes, such as straight lines, serpentine paths, U-shaped paths, etc. In the embodiment of FIG. 5E, a group of short straight well exhaust channels 165A are Well transition port 162A and the well that aligns with the small adjacent well 156 (FIG. 5A) A group of long straight well exhaust channels 165B extend between the well exhaust ports 163A and 163B. The corresponding well transition port 162B and the well 156 extend radially outward beyond the well 156. 154. The well outlet port 165B extends between the well outlet port 165B aligned with the large well 154 located at the bottom of the well. Additionally, a cache reservoir 167 is provided which is loaded and refilled at the reservoir port 162C. At various times during operation, a portion of the fluid is unloaded from the storage channel 165C. It may be desirable to store a portion of the fluid temporarily without disposing of it. The available storage channel 165C is then filled with air as needed. (or an inert fluid) can be injected and left in the reservoir channel 165C. Optionally, the port 163C may be connected to the well plate 15. 0 may be coupled to a corresponding storage well on

[0090] FIG. 5C shows a more detailed view of the fluid analysis station 170 on the back of the well plate 150. A bottom view of a portion of the base 152 is shown for illustration purposes. The fluid analysis station 170 is inserted and aligned with the optical interface. 4 includes a window 410 that is diagonally bounded by interface ports 180 and 182 at opposite corners. The interface ports 180 and 182 are connected to the flow cell through which the flow cell is inserted. When the limit posts 190 and 192 are inserted into the flow cell, they are coupled to the ports of the flow cell. The limit posts 190, 192 are located along one or more sides of the station 170. When the flow cell is inserted, it engages with the flow cell and connects the flow cell to the optical interface. Proper alignment in the XY direction with respect to the window 410 and the interface ports 180, 182 .

[0091] The back surface of the well plate 150 extends outward (downward) from the bottom surface of the well plate. The rib 472 includes a rib 472. For example, the rib 472 is aligned with the extension of the rib 412 (FIG. 5D) in the opposite direction. The bottom surface of the well plate 150 also includes a Z location pad 473. 773 and the outermost surface of rib 472 are aligned in a common predetermined plane to define a Z datum point, The Z datum point of the flow cell cartridge 900 is positioned during insertion. As will be described, the flow cell cartridge 900 includes flow cell windows and ports that are fluidly coupled to the flow cell. In order to maintain the sample at a predetermined Z position relative to the bottom of the well plate at the analysis station 170, 472. The upper frame includes an upper surface that abuts Z location pads 473 and ribs 472 for supporting the Z positioning member 470.

[0092] FIG. 5D shows a more detailed view of the fluid analysis station 170 on the top surface of the well plate 150. 5C, which provides a top view of the front / top portion of the base 152. The front / upper portion of the base 152 in the analysis station 172 corresponds to the illumination chamber (FIG. 4). Therefore, the reference numbers used in relation to FIG. 4 are also used in relation to FIG. 5D. As shown in FIG. Additionally, position limiters 408 are provided along one or more sides of the lighting station 172, By way of example only, the lighting device may be inserted into a recess by a device that engages with an engagement feature on the outer periphery of the lighting device. A dashed circle is shown to indicate the footprint of the lighting element when the position limiter 40 is 8 positions the illumination element at a predetermined XY coordinate position (where the XY coordinate system is the well plate 150 and in a plane approximately parallel to the surface of the optical interface window 410).

[0093] The well plate 150 has an optical interface window 41 on its upper surface for accommodating the illumination elements of the instrument. 0. The insertion limiting element 411 includes one or more insertion limiting elements 411 to keep the insertion limiting element 411 at a predetermined distance from 0. 1 engages with the illumination element of the instrument during microfluidic analysis operations. 11 is one or more ribs provided along one or more sides of the optical interface window 410 412, which extend upward from the optical interface window 410 to the illumination element A desired offset between the distal surface of the child (e.g., lens) and the optical interface window 410. The ribs protrude a predetermined distance determined to maintain the upper surface of the well plate 150. The top rib 412 aligns with the rib 472 on the bottom surface of the well plate 150. The lighting element is positioned at a predetermined Z tolerance position or Z coordinate position (where the Z axis of the reference coordinate system is In a plane approximately perpendicular to the surface of the well plate 150 and the surface of the optical interface window 410 As an example, the ribs 412 may be configured to align the LED light sources in the lighting element with a given surface (e.g., an optical The LED light source of the device and the optical interface window 410 are The Z tolerance between the flow cell below can be kept to a minimum.

[0094] Within the valve station 164, a select well transition port 162 ( The feed port 160 is connected to the feed pipe 162 via the feed valve 234. The port 160 is coupled to a transition port 176 via a channel 174. 76 diverts the flow direction to the opposite side of the base 152. An illumination channel 178 is shown in the fluid analysis station 170. The optical interface window 410 is located adjacent to the transition port 176. The fluid passes through the flow cell channel on the flow cell. The fluid then exits the flow cell at flow cell port 182. The fluid is transported from interface port 182 along flow cell channel 184 .

[0095] FIG. 5D also illustrates in more detail illumination channels 178 and 184 formed in accordance with one embodiment. However, the illumination channels 178, 184 are adjacent to the optical interface window 410 and have corresponding optical interfaces. The illumination channels 178, 184 terminate in interface ports 180, 182. The opening may be formed as an open-sided channel on the front surface of the chamber 150, in which case the open sides may be The illumination channel 178 is covered by a transition channel cover 416, 418 (FIG. 4). The illumination channel 184 starts at port 176 and ends at interface port 180. Starting at interface port 182, the pump station port (not visible in FIG. 5D) Ends with.

[0096] The embodiments described herein have been generally described with respect to unidirectional fluid flow. The volume analysis operations may be performed in conjunction with counter-flowing fluid flows. Additionally, the fluid can be controlled to flow in different directions in various channels at different stages of the fluid analysis. Therefore, any port, channel, or other structure can be given a name that describes the direction of flow. However, such description is merely exemplary and may not be used to refer to ports, channels, or It will be appreciated that other structures may be used to convey fluid in the opposite direction.

[0097] Syringe Pump Assembly 6A-6E, a syringe pump assembly 500 as described herein will now be described. In connection with one embodiment, a syringe pump assembly as described herein may be The Li500 offers bi-directional pump action that avoids the undesirable backlash effect The syringe pump assembly 500 applies a driving force in one direction and also applies a bias force. The plunger arm is reciprocated by allowing the plunger arm to move in opposite directions, thereby The need to apply tension to the assembly 500 is eliminated.

[0098] FIG. 6A shows a porch on a well plate 150 provided in accordance with one embodiment described herein. 1 shows a top plan view of a pump station 168. The pump station 168 has a stay at one end. a station inlet port 508 and an opposite end coupled to the station exhaust end 510 The pump channel section 506 includes a preparation section 512 and a discharge section 514. The pumping section 514 and the pumping section 516 can be functionally divided into The work sections 516 are configured to support fluid flow in both directions in series with one another. The plunger 540 includes a working area 513 where low pressure (e.g., vacuum) and high pressure are exchanged. The working area 513 is located upstream and downstream of the working area 513. The pinch valve 518 is sandwiched between a pair of pinch valves 518 located in the working area. The flow direction from the anode 513 is determined, for example, the discharge direction or the flow cell direction. The pinch valve 518 is a circular recess formed along a channel in the working section 516. can be formed by forcing the material of interest (e.g., thermoplastic elastomer) into As described herein, the pinch valve 518 may be used to control the pump station 168. Low and high pressure leads in the working area 513 to draw or push fluid through The preparation section 512 is alternately opened and closed according to the situation in relation to the entry. The station inlet port 508 is located upstream of the working section 516. In one embodiment, the preparation section 512 holds a predetermined amount of fluid before the fluid passes through the working area 516. The pump channel section 506 is arranged in a serpentine configuration to form a reservoir for holding the If desired, the preparation section 512 may be lengthened or shortened, or For example, by locating station inlet port 508 adjacent to the end of working section 516. The discharge section 514 is connected to the working section 516 and the station discharge port 518. 510 and downstream of the working section 516. 4 is provided as a relatively short straight channel, although in alternative embodiments the length and pattern may be varied. A discharge section 514 with a different drain may be provided or removed entirely.

[0099] FIG. 6B shows a side view of plunger 540 disposed within pump 500. 40 generally includes a drive arm 546 and a drive shaft 548 connected together by a bridge segment 552. ram arm 554, all of which are monolithic (e.g., one piece) The drive arm 546 has a drive end 548 and a distal end 549. Plunger arm 554 has a working end 556 and a distal end 558. The drive arm 546 and the plunger arm are attached to the working end 556 of the plunger arm. Distal ends 549 and 558 of arm 554 are coupled to bridge segment 552. The plunger arm 554 and the drive arm 546 extend from the bridge segment 552 to the plunger arm 554. The plunger arm 554 extends downward in a common direction with the drive arm 546. Since the drive arm 546 and the planar The jaw arms 554 are oriented and aligned in common in response to the drive force 543 and the bias force 544. The driving force 543 and the biasing force 544 move together without a corresponding counter-pulsive force. The bridge segment 552 is connected to the pump access hole 552 formed in the cover 102. It includes a bias surface 542 located in and exposed through the opening 123 (FIG. 1A). A biasing element (e.g., a spring) of the device engages the biasing surface 542 and applies a biasing force. The drive end 548 of the drive arm 546 is in contact with the surface 542 of the cartridge assembly 100. A drive opening 116 (FIG. 1B) is located in the bottom surface 110 and engages the pump drive assembly of the instrument. The pump drive assembly intermittently supplies drive force 543 to and from the drive arm 546. The driving end 548 and biasing surface 542 are located on opposite ends of the plunger 540. The movable end 548 and bias surface 542 are aligned with the upper surface of the housing of the cartridge assembly 100 and and exposed at the bottom surface thereof, a corresponding unidirectional actuation force is provided in conjunction with the reciprocating motion of plunger 540. Force 543 and bias force 544 can be applied to drive end 548 and bias surface 542. This avoids the introduction of backlash and allows for direct instrument-coded measurements. The driving and biasing forces 543, 544 can provide a bidirectional push system. This provides a system that eliminates the need for push / pull pump drivers.

[0100] FIG. 6C shows an enlarged side view of plunger element 557 attached to plunger arm 554. Plunger element 557 is shown partially transparent to show its internal structure. The plunger arm 554 is formed integrally with one or more stems 559 into a monolithic structure. The support includes a tip 553. The stem 559 includes a hinge pin 565 extending therebetween. The support beam 551 is provided with an eye 545 at its proximal end. The eye 545 is elongated and is hinged. Pin 565 is received by support beam 551 to support plunger arm 554 and plunger element 556. 557. The movable member 557 is movable in the direction of the arrow 567 extending approximately parallel to the length of the movable member 557. If desired, the stem and support beams 559, 551 may be formed as a common monolithic structure. You may do so.

[0101] The plunger element 557 includes a body 561 having a predetermined diameter about the circumference of the body 561. The body 561 is formed in a generally tubular shape having a constant contour. It includes a leading edge 553 and a trailing edge 555 that are formed in line (eg, by a cold forming process). The body 561 includes one or more peripheral plunger ribs 563 that are attached to the plunger arm 5 54 is shaped to maintain an airtight seal within the interior passage of the reciprocating support post 504. will be installed.

[0102] The plunger element 557 is a substantially more flexible and compressible thermoplastic elastomer than the plunger arm 554. The drive arm 546 may be made of thermoplastic elastomer (TPV) or other materials. The segment 552 and the plunger arm 554 are made of a relatively hard plastic material (e.g. The plunger element 557 is formed of a material such as a polycarbonate plastic. In one embodiment, the plunger arm 554 is formed in a non-snap-fit ​​manner. The stem 559 and the support beam 551 may be molded onto the stem 559 and the support beam 551. For example, a two-shot mold may be used. Using a bonding technique, the plunger arm 554 is molded during the initial molding process and the plunger The element 557 may be added during the second molding process. The plunger element 557 is attached to the plunger arm with a gap between them (leading edge 553 and trailing edge 555). The plunger element 557 and the plunger arm 558 are fixed together with a certain tolerance or gap between them. The fibers 554 are physically and chemically connected to each other (at leading edge 553 and trailing edge 555).

[0103] By providing close tolerances between the plunger element 557 and the plunger arm 554 Thus, the plunger 540 simply snaps the plunger element onto the plunger arm. Or, the "hysteresis" that may occur when fitting loosely in other ways is nearly eliminated. Avoided.

[0104] A non-snap-fit ​​interface between the plunger element 557 and the plunger arm 554. The plunger element moves upward and downward relative to the plunger arm each time the direction of motion changes. This provides an improvement over snap-on plunger elements that introduce the possibility of axial movement. When motion is experienced between the snap-on plunger and the plunger arm, such a structure The composition can result in backlash, also called hysteresis.

[0105] According to the embodiments described herein, the plunger 540 may be moved multiple times (e.g., once) during operation. The plunger 540 moves in both directions at 0.3 mm / s The snap-on plunger element can move at a speed of ec ~ 10 mm / sec. Backlash or hysteresis may occur multiple times during one run (microfluidic analysis operation). The embodiments described herein may include a plunger element 557 attached to a plunger arm 558. 54 (non-snap-fitting) to maintain a fixed relationship therebetween. This avoids the risk of hysteresis or backlash.

[0106] Returning to FIG. 6B, during operation, the pump drive assembly of the instrument is A driving force 543 is intermittently applied to the driving end 548 to move the plunger 540 in the direction of the driving force 543. When the driving force 543 is removed, the biasing force 544 moves the plunger 540 upward. The bias force 544 moves the actuator downward in the direction of the bias force 544. Applying force 544 attaches the pump drive assembly to drive arm 546. This avoids the need to apply a pulling force to the drive arm and the need to apply a pulling force to the drive arm. is applied and removed, thereby repeatedly moving plunger 540 upward and downward during operation. As plunger 540 moves upward and downward, working end 556 introduces low and high pressure conditions into the working area 513 (FIG. 6A). When introduced into area 513, fluid is drawn along channel segment 506 and The direction of fluid movement through the pump channel segment 506 is determined by the pinch valve. It is controlled by opening and closing.

[0107] FIG. 6D shows a side view of pump station 168 to better illustrate pump operation. Within the pump station 168, a push pin support 560 is provided to support the well plate 150. The support 560 is attached to the bottom surface of the base 152 of the support 560. The support 560 includes a support post 56 having a passage 564. 2. Passages 564 receive corresponding push pins 520, 521. The shafts 520 and 521 include a shaft 523 having a working end 566 and an opposite end 568. The working end 566 is located at the pinch valve 518, but the contact pad The shaft 524 extends radially beyond the outer edge of the support post 562. The passage 564 also includes one or more external ribs 525 therearound. The external and internal ribs 525, 527 cooperate to support the push pins 520, 521. The push pins 520 and 521 are held in a passage 564 that faces the valve opening direction 519 and The contact pad can move up and down along the support post 562 in the valve opening direction 517. Push pin hole 524 is positioned in push pin opening 114 (FIG. 1B) in bottom surface 110 .

[0108] In operation, the valve actuation element of the instrument is placed into engagement with the contact pad 524. The push pins 520 and 521 are actuated by the drive element to apply a valve closing force (in the valve closing direction 519). The valve closing force is applied to one of the push pins 520 and 521, but not to the other push pins 520 and 521. When not applied to the push pins 520, 521, the push pins 520, 521 are valve As the valve moves in the open direction 517 to an open state, the corresponding pinch valve 518 opens. When a valve closing force is applied, the corresponding push pins 520, 521 move in the valve closing direction 519. When the push pins 520 and 521 are moved, the corresponding pinch valves 518 are closed. The corresponding pinch valve 518 is alternately open and closed.

[0109] FIG. 6D also shows the plunger arm 554 when loaded into the support post 504. The jaw arm 554 reciprocates in a pull direction 566 and a push direction 568 to cover the working area 5 13. The plunger arm 554 is pulled in the pull direction 56 6, fluid is drawn into and drawn into the working area 513. The amount of fluid pumped is determined by the range of motion of the plunger arm. When the flow moves in the flow direction 568, the fluid in the working area 513 is forced out of the working area 513. The fluid is drawn from the fluid channel into the working area 513. The direction depends on which of the push pins 520, 521 closes the corresponding pinch valve 518. For example, to introduce a pulling force in the direction of arrow A, the syringe arm must be in the pulling direction. 566, the push pin 521 closes the corresponding pinch valve 518. As the plunger arm 554 is retracted from the working area 513, As the plunger arm 554 moves, the fluid advances along the fluid channel in the direction of arrow A. Upon reaching the end of its range of motion, the push pin 521 is released and allowed to move in the opening direction 517. is permitted to open the corresponding pinch valve 518. 20 moves in the closing direction 519 to close the corresponding pinch valve 518. The arm 554 moves in a push direction 568 to push the fluid from the working area 513 into the fluid channel. Push the fluid into the pipe in the direction of arrow B. If you want to move the fluid in the opposite direction, use the push pin. The operations of 520 and 521 may be reversed with respect to the movement of the plunger arm 554.

[0110] FIG. 6E shows an enlarged side view of a portion of plunger 540 inserted into support posts 502, 504. A plunger arm 554 is slidably received within the support post 504 and is driven by the plunger arm 554. The movable arm 546 is slidably received within the support shaft 502. The drive arm 546 drives the plunger 540 along a predetermined reciprocating path with relatively small tolerances. It is formed with an X-shaped cross section to accommodate the inside.

[0111] FIG. 6F illustrates a support shaft housing a plunger arm according to embodiments described herein. 5 shows a perspective view of the support shaft 504. The support shaft 504 includes a proximal end 570 and a distal end 571. The proximal end 570 is attached to the well plate 150, while the distal end 571 is attached to the pump station. The support shaft 504 is elongated and has a proximal end 570 and a distal end 572. 571. The passage 572 extends from the distal end 571 to the proximal end 57 The passage 572 has a first inner diameter 571 at a section thereof that extends toward a portion proximate zero. Passage 572 terminates at proximal end 570 with a second enlarged portion to form parking station 574. The parking station 574 has a diameter 576. When placed in a storage position, the parking station 574 is The plunger element 557 receives at least a portion of the plunger rib. They may be placed in parking stations 574 during storage, transportation, or generally when not in use. Holding the plunger rib of the plunger element 557 in a parking station having a large diameter By enabling, the embodiments described herein prevent creep of the plunger element 557. To avoid this, the plunger element 557 and the plunger ribs are not overly compressed. The plunger element 557 and the plunger If the jarib is stored for an extended period of time within the portion of the passageway 572 having the first narrow diameter 575 , creep (or change in shape) may occur.

[0112] fluid equipment FIG. 7 illustrates a block diagram of a fluidic device 700 implemented in accordance with embodiments described herein. The device 700 includes a docking station 70 that houses the cartridge assembly 100. 3. Various electrical, optical and mechanical subassemblies within the device 700 are microfluidic The cartridge assembly 100 interacts with the patient during a somatic analysis procedure.

[0113] The device 700 includes, among other things, one or more processors 702, which may include a microfluidic The processor 704 executes program instructions stored in memory 704 to perform system analysis operations. The processor 702 includes a valve drive assembly 710, a pump drive arm 720, a drill actuator, and a An air assembly 740, a lighting element 750, an electrical contact array 752, and a heating element 753. is communicatively coupled to

[0114] A user interface (U / I) 706 allows a user to control and manage the operation of the device 700. One or more communication interfaces 708 are provided for communication between the device 700 and a remote controller. It conveys data and other information between computers, networks, etc. For example, a communications interface The interface 708 receives protocols, patient records, and other information related to a particular fluid analysis operation. The communication interface 708 communicates the raw data obtained as well as the results of the analysis of one or more samples. It also communicates derived data.

[0115] The valve drive assembly 710 is a drive shaft 7 which engages the rotary valve assembly 200. 12. The valve drive assembly 710 also includes a rotational motor 714 and a translational motor 716. The translation motor 716 rotates the drive shaft 712 to rotate the rotor shaft of the valve assembly 200. The drive shaft 712 rotates in a translational direction between an engaged state and a disengaged state. When firmly physically engaged with the valve assembly 200, the rotary motor 714 drives the drive shaft. The rotation of the rotary valve assembly 200 is controlled to rotate in a direction 719 of the rotation of the valve 712 to allow the rotary valve assembly 200 to accommodate various reagents. The wells are instructed to be connected or disconnected to channels in the well plate.

[0116] The valve drive assembly 710 is connected to the rotor shaft 202 (FIG. 2B) of the drive shaft 712. The encoder 713 monitors the position of the drive shaft relative to the 712 and the internal splines of the rotor shaft 202. The position data is provided to the processor 702 for positioning the This ensures close tracking of the rotational position of the rotor shaft 202. The driver 713 is connected to the internal splines 232 (see FIG. 2B) with male encoder spline structure shaped and dimensioned to match The encoder splines may include a shaft to maintain a constant relationship between them. The encoder spline is formed into the internal spline 232 until it bottoms out. Instead, it simply follows the rotor shaft 202 to generate precise and accurate angular position data. The drive shaft 712 fits onto the distal end of the rotor shaft 202. The drive splines include another set of drive splines that mate with each other. The drive splines mate with each other to transmit the drive force to the load. The axially extending shaft 202 feeds into an external spline on the axially extending shaft 202 .

[0117] By maintaining the rotor shaft 202 and the drive shaft 712 in a constant rotational relationship The processor 702 uses the rotation data obtained from the motor 714 to control the rotor valve 234. The specific rotational position of can be determined.

[0118] The valve actuation assembly 710 selectively connects the flow channel to one or more ports. In many operations, the rotor shaft 202 is moved (rotated). The motor shaft 202 is aligned based on the position of the well ports for the reagent wells that are used successively. For example, when adjacent wells are used in sequence, the valve is driven The rotor assembly 710 rotates the rotor shaft 202 by a few degrees. When first and second wells on opposite sides of the well are used, the valve actuation assembly 710 Rotate the rotor shaft 202 by 180° or nearly 180°. After rotation, the rotary valve assembly 200 temporarily stops, preventing fluid from flowing or This allows the sample to be detected.

[0119] The drill actuator assembly 740 includes one or more drill shafts 742 and a drill and a translation motor 744 that drives the machine shaft 742 between a retracted position and an extended position. When the drill shaft 742 is moved to the extended position, the drill shaft 742 is 300 and pushes the punch unit 300 downward to The perforation element is capable of perforating the foil covering the corresponding reagent well. 742 may remain extended or may be retracted during the fluid analysis operation.

[0120] The pump drive assembly 720 includes a pump shaft 722 coupled to a motor 724. The pump shaft 722 moves along a pump direction 723 between an extended position and a retracted position. As an example, the pump shaft 722 is a screw shaft that rotates in the direction of the arrow 721. By changing the twisting direction of the pump shaft 722, the pump shaft The shaft 722 moves inward (retraction direction) or outward (extension direction) along the pump direction 723. By repeatedly moving the pump shaft 722 between the retracted position and the extended position, Thus, the pump shaft 722 provides a driving force 543 to the drive arm 546 to drive the pump assembly. 500 to aspirate / draw fluid into the pumping station. 54 in a direction that creates a low pressure condition in the working area. position so that biasing element 734 is biased against biasing surface 55 of pump assembly 500. 42 to rotate the pump assembly 500 downward in the direction of bias force 544. 544 to create a high pressure condition in the working area and pump the The fluid is dispensed from the dispense station.

[0121] A position encoder 735 is also provided on the bias element 734. The position encoder 735 The position of biasing element 734 changes as the biasing element moves up and down with plunger 540. The position encoder 735 provides position data to the processor 702 for planning purposes. The position of the JA 540 is tracked during operation.

[0122] The pump drive assembly 720 is a spring that is positioned to align with the push pins 520 and 521. The valve drive shafts 726 and 728 are connected to the motor 730 moves along arrow 725 between the extended and retracted positions. The valves 726, 728 are moved in opposite directions, and when the valve drive shaft 726 is extended, The valve drive shaft 728 is retracted and vice versa. 28 for pumping fluid through pump station 168 and thus through the flow cell. , are alternately moved in opposite directions in synchronization with the movement of the pump shaft 722.

[0123] The lighting elements 756 enter and exit the illumination chamber 400. The lighting elements 750 include one or more The illumination chamber 400 includes an optical system that provides the above types of illumination light within the illumination chamber 400. The element 756 may include LED light tubes or the like to produce the desired amount and type of light. The electrical contact array 752 and the heating element 753 are disposed on the bottom surface 1 of the cartridge assembly 100. 10. The contact array 75 is inserted into the flow cell cartridge access area 112 in the flow cell cartridge 10. 2 engages with a corresponding array of electrical contact pads on the flow cell cartridge 900. The member 753 engages with a heat spreader in the flow cell cartridge 900 .

[0124] In accordance with at least one embodiment, the processor 702 controls the motors, optics, contact array, Optionally, the motor, assembly, etc. described in connection with the device 700 may be , to manage the operation of each of the optical systems, contact arrays, assemblies and components ( For example, multiple processors acting in cooperation (under the control of processor 702) may be provided.

[0125] For example, the motor may be a DC drive motor. However, various alternative mechanisms, e.g. Direct current (DC) motors, solenoid drivers, linear actuators, piezoelectric motors, etc. May be used.

[0126] Fluid Control Systems FIG. 8 illustrates a computer system 81 implemented in the device 700 of FIG. 7 according to one embodiment. 8 shows a schematic diagram of a computer system 810 that includes one or more processors 702. 708 and the program instructions stored in the memory 704. FIG. 8 illustrates various components of a computer system 810. 8 shows a representative diagram or block diagram of the components, but FIG. 8 is merely a schematic diagram or example, and It should be appreciated that the computer system 810 may take a variety of forms and configurations.

[0127] The computer system 810 may include various components, assemblies and systems of equipment. (or subsystem). The computer system 810 is capable of communicating with a fluid selector Module 851, fluid control module 852, detector module 853, protocol module module 854, analysis module 855, pump drive module 857, valve drive module Modules 851-861 may include a lighting control module 859, and a lighting management module 861. Although shown as separate blocks, each of the modules may be implemented in hardware, software or may be a combination of both and each of the modules may be the same component, e.g. It should be understood that the modules 851-852 may be part of, for example, a processor. At least one of the modules 851 may be part of another processor. Each of the -861 may be able to communicate with each other and receive commands / instructions to perform specific functions. The laws may be consolidated.

[0128] The computer system 810 and / or modules 851-861 may be processor-based. or microprocessor-based systems, e.g., microcontrollers, reduced instruction set computer (RISC), application specific integrated circuit (ASIC), field program FPGAs, logic circuits, and any other suitable devices capable of performing the functions described herein. The above embodiments are merely examples. and does not necessarily limit the definition and meaning of the terms module or computer system. In an exemplary embodiment, computer system 810 and / or Alternatively, modules 851-861 may generate samples, acquire detection data, and / or generate detection data. instructions stored in one or more storage elements, memories, or modules for analyzing the data; Perform a set.

[0129] The set of instructions instructs the device 802 to perform the methods and processes of the various embodiments described herein. A set of instructions may contain various commands that cause a software program to perform a particular operation, such as a program. The term "software" and "file" as used herein may be in the form of a "Firmware" is interchangeable and is stored in RAM memory for execution by a computer. ROM memory, EPROM memory, EEPROM memory and non-volatile RAM (NVR Any computer program stored in a memory, such as a memory for storing the above-mentioned programs. The types of memory are merely examples and are not intended to limit the types of memory that are useful for storing computer programs. This does not limit the type.

[0130] Software includes various types of software such as system software and application software. Further, the software may be in the form of a collection of separate programs, or a larger program. The software may be in the form of a program module or a part of a program module. The software includes modular programming in the form of object-oriented programming. Good too.

[0131] Although computer system 810 is shown conceptually as a collection of modules, it is not limited to dedicated It can be implemented using any combination of hardware boards, DSPs, processors, etc. Alternatively, the computer system 810 may be an off-the-shelf computer having a single processor. Using a shelf PC or having multiple processors, the functional operations are distributed among the multiple processors. As a further option, the implementation may be implemented using an off-the-shelf PC that is capable of The above module functions are implemented using dedicated hardware. However, the remaining module functions are executed using an off-the-shelf PC, etc. The modules may be implemented using software modules in a processing unit. One or more of the computing modules may be implemented, for example, in a network or in a cloud. The system may be located within a distributed computing environment.

[0132] As described herein, the valve drive assembly and the pump drive assembly correspond Indicates the rotational and translational positions of components that rotate (e.g., rotating valves and plungers) The signal processor 812 includes an encoder that transmits a signal to the computer system 810.

[0133] In some embodiments, the detector module 853 is an imaging assembly (illumination element The imaging window (interface 750 and the analysis circuit in the flow cell cartridge) 4, a portion of the transparent layer of the flow cell window 410, the flow cell window 928, and the analysis circuit 958 is imaged. This command directs the incident light to the excitation source (illumination element) through the interface window. to excite labels in the sample within the active area of ​​the analysis circuit 958. Module 853 communicates with analysis circuitry 958 via contact array 752 and contact pads 950. In the case of SBS sequencing, each image is a DNA cluster. As shown in the figure, the fluid selector module 851 includes a number of point light sources. The valve actuation assembly can be commanded to move the rotary valve assembly. A control module 852 commands the various pumps and valves to control the flow of fluids. The protocol module 854 executes a system so that a specified protocol is executed. The protocol module 854 may include instructions that regulate the operation of the system 800. The control element can also be commanded to control the temperature of the fluid. The Cormodule 854 acts as a sequencing by synthesis (SBS) module. Issue various commands to run the sequencing-by-synthesis process. In some embodiments, the protocol module 854 processes the detection data. After generating amplicons by bridging PCR, protocol module 8 54 contains instructions and sequences for linearizing or denaturing the amplicon to generate sstDNA. Add a sequencing primer to the uniplex that flanks the region of interest. Each sequence provides instructions for hybridizing to a generic sequence. The binding cycle extends the sstDNA by a single base, which is achieved by protocol module 854 The delivery of a mixture of modified DNA polymerase and four types of nucleotides that can be directed by This is achieved by feeding different types of nucleotides with unique fluorescent labels, and each Nucleotides are reversible terminators that can only undergo single base incorporation in each cycle. After a single base is added to the sstDNA, the protocol module 854 A washing step is performed in which a wash solution is passed through the flow cell to remove unincorporated nucleotides. The protocol module 854 further instructs the excitation source assembly and The detector assembly is then fed with fluorescence in each of the four channels (1 for each fluorescent label). After imaging, protocol module 8 54 commands the delivery of a deblocking reagent to remove the fluorescent label and terminator from the sstDNA. The protocol module 854 can be chemically cleaved from the unblocking reagent. and a washing step to remove the products of the deblocking reaction can be ordered. Other similar sequencing cycles can follow.

[0134] Exemplary protocol steps that may be coordinated by protocol module 854 include reversible timing. The fluidics and detection steps used in the inductor-based SBS method are included. The methods are described, for example, herein and in U.S. Patent Application Publication No. 2007 / 0166705. , U.S. Patent Application Publication No. 2006 / 0188901, U.S. Patent No. 7,057,026, U.S. Patent Application Publication No. 2006 / 0240439, U.S. Patent Application Publication No. 2006 / 281 109, PCT International Publication No. 05 / 065814, U.S. Patent Application Publication No. 2005 / 100 No. 900 and PCT Publication No. WO 07 / 010251, each of which is incorporated herein by reference. The entire contents of which are incorporated herein by reference. Representative reagents for this purpose are described in U.S. Pat. No. 7,541,444, U.S. Pat. No. 7,507, No. 7,427,67 No. 3, U.S. Patent No. 7,566,537, U.S. Patent No. 7,592,435 and WO 07 / 135368, each of which is incorporated herein by reference. , which is incorporated herein in its entirety. Commercially Available Sequencing Platforms GA, Hi, available from Ilamina, Inc. (San Diego, Calif.) Protocols used on the Seq® and MiSeq® platforms Colstep and reagents can also be used.

[0135] In some embodiments, the protocol module 854 performs a pyrosequencing process. You can issue various commands to execute steps in the protocol. The method includes the steps described below and in the following references: Synchrotron radiation is a process that occurs when a specific nucleotide is incorporated into a nascent nucleic acid chain by the action of inorganic pyrophosphate (PP i) Detect the release of β-amyloid (Ronaghi, et al. "Real-time DNA sequencing using detection of pyrophosphate release” (1996), Analytical Biochemistry 242(1), 84-9;Ronaghi ,M. (2001), “Pyrosequencing sheds light on DN sequencing”, Genome Res.11(1), 3 -11;Ronaghi et al. (1998) “A sequencing method based on real-time pyrophosphate " Science 281(5375), 363; U.S. Patent No. 6,210,891; U.S. Patent No. 6,258,568 Nos. 6,274,320 and 6,274,320, each of which is incorporated herein by reference. In pyrosequencing, the released PPi is converted to ATP It is detected by its immediate conversion to adenosine triphosphate (ATP) by phosphodiesterase. The amount of ATP produced can be detected via luciferase-generated photons. In this case, the reaction valve 816 can contain millions of wells. Each well contained a single capture bead with clonally amplified sstDNA on it. Each well can also contain other smaller beads, which can be, for example, solid Immobilized enzymes (e.g., ATP sulfurylase and luciferase) are delivered or captured in the wells. The protocol module 854 can facilitate retention of capture beads of a single type. Successive cycles of nucleotide-carrying fluid (e.g., 1st cycle: A; 2nd cycle: G; Cycle 3: C; Cycle 4: T; Cycle 5: A) When a nucleotide is incorporated into DNA, pyrophosphate is released, This sets off a chain reaction that produces a burst of light, which is then sent to the detector assembly. The detected data is sent to the analysis module 855 for processing. You can be notified.

[0136] In some embodiments, a user provides user input via a user interface. In another embodiment, the assay protocol to be executed by the system can be selected based on the The system automatically detects the type of flow cell cartridge inserted into the instrument 802. Alternatively, the system can A limited number of assays can be performed for a given type of flow cell cartridge. Protocols may be provided and the user may select the desired assay protocol. The system then executes the selected assay protocol based on preprogrammed instructions. It can be executed.

[0137] The analysis module 855 analyzes the detection data obtained by the analysis circuit in the flow cell cartridge. Although not shown, the device has a user interface that allows the user to interact with it. For example, a user interface may display or request information from a user. The device may include a display for displaying the image and a user input device for receiving user input. In an embodiment, the display and the user input device may be the same device (e.g., a touch-sensitive interactive display).

[0138] In some embodiments, the nucleic acid can be attached to a surface and sequenced prior to or after sequencing. The protocol module 854 controls the flow of the fluid involved in the amplification process. Instructions for the steps used to form a population of nucleic acids on a surface may also be included. Instructions for the bridge amplification technique to be used may also be provided. Useful bridge amplification methods include, for example, No. 5,641,658; U.S. Patent Publication No. 2002 / 0055100 U.S. Patent No. 7,115,400; U.S. Patent Publication No. 2004 / 0096853 Amplifying nucleic acids on a surface is described in U.S. Patent Publication No. 2008 / 0009420. Another useful method is rolling circle amplification (RCA), e.g., as described by Lizardi et al. , Nat. Genet. 19:225-232 (1998) and US2007 / 0099 208A1, each of which is incorporated herein by reference. Emulsion PCR on beads can also be used, e.g., Dressman et al., Proc. .Natl.Acad.Sci.USA100:8817-8822(2003), International Publication No. 05 / 010145, or U.S. Patent Publication No. 2005 / 0130173 or No. 2 As described in US Pat. No. 5,999,343, filed on Nov. 23, 2005, and US Pat. No. 5,999,343, each of which is incorporated herein by reference. No. 6,399,433, which is incorporated herein in its entirety.

[0139] In some embodiments, the system operates with minimal user intervention. The synthesis and analysis operations can be performed automatically by the assay system. In this mode, the user loads the cartridge assembly and starts the instrument to run the protocol. That's all you need to do.

[0140] Flow Cell Cartridge The flow cell cartridge 900 is then adapted for at least one embodiment described herein. Therefore it is used.

[0141] FIG. 9A illustrates a flow cell cartridge 90 formed in accordance with one embodiment described herein. 9 shows a top perspective view of the flow cell cartridge 900. The flow cell cartridge 900 is generally Top and bottom frames 904 and 905 form a generally rectangular structure elongated in the loading direction 9A. The loading direction 9A is the flow cell cartridge 900 is inserted into the cartridge assembly 1 00 in the flow cell chamber 108. The housing 900 includes a loading edge 908, a trailing edge 910, and side edges 912. To ensure proper alignment in the XYZ directions within 108, the loading edge 908 and and side edges 912 are aligned with corresponding flow cell chambers 108 of cartridge assembly 100. The mounting mechanism includes one or more positioning features that engage with a mounting feature.

[0142] Optionally, the top and bottom frames 904 and 906 may be secured to, for example, electrostatic discharge (ESD) protection. It may be made of a conductive plastic to provide protection.

[0143] Optionally, the upper frame 904 may include a series of protruding members extending upwardly from the upper frame 904. The gripping mechanism 920 may include gripping features such as ribs. The gripping mechanism 920 may be configured to allow the gripping mechanism 920 to be gripped by a user. This makes it easier to grip the frame cartridge 900. The grooves provide the user with information regarding the direction in which the flow cell cartridge 900 should be inserted. Thus, the ribs may be shaped to provide a directional indication, for example by forming them in the shape of an arrow.

[0144] FIG. 9B better illustrates the optical fluidic (OF) interface of the flow cell cartridge. 9A and 9B are enlarged views of a portion of the upper flow cell 904. The upper flow cell 904 accommodates the optical components and fluids of the cartridge assembly 100. It includes an OF interface 940 for communicating with the component. The interface 940 is connected to an analysis circuit (FIGS. 9D and 9E) housed within the flow cell cartridge 900. The flow cell includes a flow cell window 928 that aligns with the flow cell 922 (described in more detail below in connection with E). The flow cell window 928 allows light from the instrument's illumination element to be directed to the analysis circuitry. 28 may be made of glass or a similar transparent material, with the glass window located above the upper flow cell 904. The glass is placed in the flow cell window 928 and is approximately coplanar with the top surface of the upper frame 904. By maintaining a planar orientation, the Z position of the flow cell window 928 is aligned with the position of the top surface of the top surface 904. By monitoring the position, more accurate monitoring can be achieved.

[0145] Flow cell port 934 is located adjacent to flow cell window 928 and 34 transports fluid from the cartridge assembly 100 through active areas in the analysis circuit. The port 934 is provided in an elongated gasket seal 930. In an embodiment, the gasket seals 930 extend generally parallel to one another and are generally parallel to the loading direction 9A. The flow cell port 934 in the gasket seal 930 is positioned at an acute angle to the cartridge. Positioned to mate with a corresponding port in the flow cell chamber 108 of the assembly 100 do.

[0146] Seals 930 are provided on opposing sides of the flow cell window 928. In one example, seal 930 The seals 930 may be disposed diagonally opposite each other across the flow cell window 928. The seal 930 may be made of a flexible elastomer or other similar material. During the manufacturing process, The TPE is injected through injection gate 932 until it forms into seal 930. The injection molding process allows the flow of air through the internal channels in the upper frame. 30 is physically and chemically bonded to the upper frame 904 to form a seal 930 on the upper frame. 904. Gasket seal 930 is low profile and Providing a compact seal structure and resulting in assembly with desired tolerances (e.g., minimizing assembly tolerances) vinegar.

[0147] Returning to FIG. 9A, the upper frame 904 is in common (e.g., parallel) with the loading direction 9A. ) direction. The ribs 922 are oriented to extend in the flow cell. When the cartridge 900 is loaded into the flow cell chamber, the gasket seal 930 and the flow cell port 934 contacts the housing mechanism surrounding the flow cell chamber 108. In addition, ribs 922 provide a standoff or non-engagement mechanism. A flow mechanism is also provided to mount the flow cell cartridge 900 upside down on a table or other structure. When the flow cell is placed on the upper frame 904, the rib 922 is arranged to prevent other mechanisms on the upper frame 904 from This helps prevent the Cartridge 900 from coming into contact with dust and other materials on the surface on which it is placed. Cut.

[0148] The upper frame 904 connects the LED light tubes in the instrument's illumination element to the flow cell cart. One or more ridges 900 are used to align the flow cell window 928. The upper surface of the upper frame 904 includes a Z position mechanism (corresponding to the Z reference point). The flow cell cartridge is abutted against the ribs 472 and pads 473 on the bottom surface of the flow plate 150. The Z position limiting mechanism defines the Z reference point for the edge 900. Provide the desired tolerance between the flow cell and the cartridge.

[0149] FIG. 9C shows a bottom perspective view of the flow cell cartridge of FIG. 9A. One or more standoffs 914 located near the loading edge 908 and the trailing edge 910 If desired, the standoffs 914 may be formed at other locations on the bottom frame 906. Additionally or alternatively, more or fewer standoffs 914 may be used. The standoffs 914 are provided to connect the mechanism in the bottom frame 906 to the flow cell cartridge. The cartridge 900 maintains a predetermined distance from any surface it is placed on. When storing the Edge 900 on a desk, lab bench, in storage, or elsewhere, the standoffs 914 are The mechanism of the main frame 906 is prevented from coming into contact with dust and other particulate matter on a desk, laboratory bench, etc. In addition, the standoffs 914 prevent the flow cell cartridge 900 from being Alignment key to prevent incorrect (e.g., backward) insertion into assembly 100 For example, the standoffs 914 may be of different sizes, e.g. For example, they may be formed to different lengths, thicknesses, standoff heights, etc. In the embodiment of FIG. The length of the standoff 914 adjacent the loading edge 908 is 10 is short in comparison to the length of the standoff 914 adjacent thereto.

[0150] The bottom frame 906 is connected to the optical-fluidic interface 940 (and The PCB 952 includes an aperture 944 that aligns with a heat spreader 955 on the PCB 952. The aperture 944 is connected to the analysis circuit. The bottom frame 906 exposes the back surface of a portion of the contact pad 9 on which the analysis circuit is provided. It also includes contact pad openings 946 that align with and expose the array of 50. 946 are separated by a crossbar 948 which extends the width of the contact pad opening 946. , unwanted objects (e.g., the user's The size of the contacts must be kept small enough to prevent accidental insertion of objects (fingers, test equipment, etc.). 9, the contact pad openings 946 are rectangular and each expose two or more rows of contact pads 950. do.

[0151] FIG. 9D illustrates a flow cell cartridge 9 formed in accordance with one embodiment described herein. 9 shows a top view of a portion of a printed circuit board 952 mounted in the NI 9000. 952 includes a top surface 956 that includes an analysis circuit 958. In one example, the analysis circuit 958 is a CMO The analysis circuit 958 represents an active area that receives incoming light from an illumination source within the instrument. Supports the flow of fluid across the 962 and detects fluorescent light emitted from the fluid in conjunction with the fluid analysis process. The analysis circuit 958 detects and obtains a digital image of the light. 62. Fluid is introduced into the active area through one of the active area ports 964. 962 and the fluid exits the active area through another one of the active area ports 964. The analysis circuit 958 emits through the flow cell window 928 (and through window 410 in FIG. 4). The active area 962 includes a transparent top surface for receiving incoming light. The incoming light illuminates the fluid within the active area 962. In response, reagents in the fluid emit fluorescence within different fluorescence spectra depending on the properties of the sample. The analysis circuit 958 detects the emitted fluorescence spectrum, obtains an image thereof, and The image is then sent to the instrument through contact pad 950.

[0152] FIG. 9E is a schematic diagram of the printed circuit board of FIG. 9D formed in accordance with one embodiment described herein. 952 shows a bottom view of the PCB 952. The PCB 952 shows an array of contact pads visible through the contact pad openings. In this embodiment, the array of contact pads 950 is formed into a number of rows. Other contact array configurations may be used as desired. Contact pads 950 are The socket connector 953 is connected to a corresponding pin in the upper surface 956 (FIG. 9D). ) and the socket connector 953 securely connects the analysis circuit 958 to the Provides power, data and communication connections between the receiving and analyzing circuitry 958 and the contact pads 950 do.

[0153] Bottom surface 954 includes a circuit contact surface (not visible in FIG. 9D) that abuts the bottom surface of analysis circuit 958. The heat spreader 955 also includes a heat spreader 955 that fits within the opening 944 in the bottom frame 906. 9C. During operation, the heating element of the device is contacted with the opening 94. 4 and contacts the heating element contact surface 957 of the heat spreader 955 to provide the desired amount of heat to the analysis circuit. It will be supplied to 958.

[0154] The printed circuit board 952 also includes a recess 957 disposed about its periphery. and a printed circuit board 952 that fits with corresponding mechanisms in the bottom frames 904 and 906. are positioned at specific locations within the top and bottom frames 904 and 906 .

[0155] The top and bottom frames 904 and 906 support the flow cell chamber 10. One or more XY positioning mechanisms (XY reference points) used to align the cartridge 900 The XY positioning mechanism includes a front reference post at the loading end 908. 923 and one or more lateral reference posts along one or both edges 912 925. A notch 927 is provided in the side edge 912 opposite the lateral reference post 925. do.

[0156] During the loading operation, the loading end 908 is mounted in the flow cell chamber 108 with a reference post 923 . A limiting mechanism within the flow cell chamber 108 that limits movement in the filling direction 9A (also called the X-direction) The flow cell cartridge 900 is inserted until it is firmly abutted against the flow cell cartridge 900. The bias arm passes over the side edge 912 that includes the notch 927, and the latch element passes over the notch 927. 7. The latching element is shaped to match the shape of notch 927. The bias arm exerts a lateral force (also represented as a lateral positioning force) in the direction of arrow 9C, causing the flow The cell cartridge 900 is fitted with a lateral reference post 925 within the flow cell chamber 108. Shift it laterally (corresponding to the Y axis) until it engages with the mechanism. Lateral reference post 92 When the flow cell chamber 108 is engaged with the engaging mechanism, the flow cell chamber 108 defines the movement limit in the lateral direction 9C. The bias arm positions the flow cell cartridge 900 at the desired Y position (corresponding to the Y reference point). The latch element of the bias arm engages with notch 927 in position. The flow cell cartridge 900 is maintained at a desired X position (corresponding to the X reference point).

[0157] When the flow cell cartridge 900 is inserted into the XYZ reference point, the communication connector ( In the Z direction, within the contact pad opening 946, the mating contact array of the communication connector is contact pad 9 50 until it engages. The communications connector provides power, collects data, and It controls the operation of the analysis circuitry within the cell cartridge 900. Additionally, a heating element is connected to the heat spreader 95. 5 is inserted (in the Z direction) into opening 944 until it engages with

[0158] Additional embodiments: Embodiment 1: In a cartridge assembly, a flow cell chamber for receiving a flow cell a housing including a member; and a well plate having a liquid well for receiving a desired amount of liquid. wherein the well plate includes a valve station, a pump station, and a fluid analysis station. the well plate includes the wells, the valve station, and a pump station and a channel associated with said fluid analysis station. a pump provided on the well plate in the pump station; a pump assembly, the pump assembly being connected to the pump station and the fluid analysis step; a pump assembly for controlling fluid flow through a channel between the pump and the station; a rotary valve assembly provided above the well plate at a valve station; The rotary valve assembly is configured to rotate about a rotary axis to move the well to the pump stem. a rotor shaft and a rotor valve configured to selectively couple to a rotor shaft and a rotor valve, a rotor shaft extending through the housing and exposed to the rotor shaft; a distal end having a the rotor shaft including a dual spline structure at the distal end, the dual spline structure has first and second sets of splines, the first set of splines forming a drive interface. and the second set of splines forms a position-coded interface.

[0159] In the cartridge assembly of embodiment 1, The distal end extends into a shaft well in the housing, thereby The double spline structure is exposed to a valve drive assembly of a fluid analysis instrument.

[0160] Embodiment 3: The cartridge assembly of embodiment 1, wherein the first set of splines corresponds to an external spline extending around the outer surface of the distal end, and adjacent splines The in side surfaces are spaced apart by a first predetermined spline spacing, the spline spacing being It corresponds to the spline pattern on the assembly drive shaft.

[0161] Embodiment 4: The cartridge assembly of embodiment 1, wherein the second set of splines an internal spline formed around the inner surface of a cavity at the distal end of the rotor shaft; The internal splines correspond to adjacent sides that are at a predetermined non-balanced angle with respect to each other. adjacent sides meet at a bottom to form a valve actuating articulation A recess is formed to receive a corresponding spline on the drive shaft of the assembly.

[0162]

[0021] Embodiment 5: The cartridge assembly of embodiment 1, wherein the rotor valve is coupled a flange attached to the proximal end of the rotor shaft, the coupling flange being A predetermined amount of tilting is permitted between the rotor valve and the rotor shaft.

[0163] Embodiment 6: The cartridge assembly of embodiment 4, wherein the rotor valve is a rotor base having one or more ribs disposed about a proximal end of a rotor shaft; The mating flange is retained between the rib and the proximal end of the rotor shaft.

[0164] Embodiment 7: The cartridge assembly of embodiment 1, wherein the rotor valve is a central a well plate contact surface having a central port and a radial port, A channel extends radially outward from the core port to the radial port.

[0165] Embodiment 8: The cartridge assembly of embodiment 6, wherein the central port is The axis of rotation of the motor shaft is aligned with the center feed port of the well plate. The rotor valve is aligned to rotate about the rotation axis to move in the radial direction. Align the wells with the corresponding well ports.

[0166]

[0023] Embodiment 9: The cartridge assembly of embodiment 1, wherein the rotary valve is an interface valve. a well plate contact surface formed by an interface ring, the interface ring being attached to the well plate contact surface; It extends around the periphery of the contact surface.

[0167] Embodiment 10: The cartridge assembly of embodiment 1, wherein the rotary valve is rotated. a valve cap including an internal cavity for operably receiving said valve; One or more labels are attached to the wells, with the labels facing downwardly relative to the well plate. The bias element further comprises a bias arm and is disposed within the internal cavity. The biasing element applies a bias force to the rotary valve to bias the port of the rotary valve and the well. Maintain a sealed interface between the rate port.

[0168] Embodiment 11: The cartridge assembly of embodiment 1, wherein the pump assembly The plunger includes a drive end and a bias surface at each end of the plunger, The bias surfaces are exposed on the top and bottom surfaces of the housing and are adapted to engage with the reciprocating motion of the plunger. Corresponding unidirectional drive and bias forces are applied in series to the drive end and bias surface.

[0169] Embodiment 12: The cartridge assembly of embodiment 11, wherein the plunger is a plunger. Ridge segments are interconnected in a U-shape and integrally formed into a monolithic structure. A drive arm and a plunger arm are provided, the drive arm and the plunger arm being connected to the The well plate is housed within a support post located on the well plate.

[0170] Embodiment 13: The cartridge assembly of embodiment 11, wherein the plunger is a different The plunger arm and plunger element are integrally molded from a material.

[0171] Embodiment 14: The cartridge assembly of embodiment 13, wherein the plunger element is formed at the tip of the plunger arm, and the plunger element is The coils move in corresponding support posts to generate high and low pressures at the coils.

[0172] Embodiment 15: The cartridge assembly of embodiment 1, wherein the pump station The system includes a channel section that is functionally divided into a preparation section, a discharge section, and a pumping section; All of these sections are configured to be continuous with one another and to support fluid flow in both directions. .

[0173] Embodiment 16: The cartridge assembly of embodiment 1, wherein the pump station The work area is sandwiched between a pair of pinch valves placed upstream and downstream of the work area. the pump assembly includes a plunger aligned with the working area, the plunger The pump assembly is reciprocated relative to the working area to introduce high and low pressure conditions. The actuator further comprises a push pin aligned with the pinch valve, the push pin being arranged to move in an alternating manner. The pinch valve is opened and closed by moving the switch.

[0174] Embodiment 17: The cartridge assembly of embodiment 1, wherein the housing includes a The method further comprises the steps of: providing a drilling unit that is supported by the well and is positioned adjacent to the well; The punching machine unit includes a punching element, and when the punching machine unit is moved to a punching position, the punching element is opposed to the punching machine unit. Drill holes in the covers of the corresponding wells.

[0175] Embodiment 18: The cartridge assembly of embodiment 17, wherein the housing further comprises: A cover having a drill access opening providing equipment access to an upper end of the drill unit. Includes.

[0176] Embodiment 19: In the embodiment of embodiment 17, the drilling unit is a body formed like a conical tube having a bottom form, a middle portion and an upper flange; At least one of the bottom platform or the top flange has perforations distributed in a predetermined manner. a piercing element arranged to align with the wells of the well plate. can be.

[0177] Embodiment 20: The cartridge assembly of embodiment 1, wherein the rotor shaft a platform that fits around the piercing element, the platform supporting the piercing element; Engage with the engagement feature of the rotary valve assembly to align with a corresponding well. An indexer for positioning the drill unit at a predetermined rotational orientation relative to the rotor shaft. Includes the mechanism.

[0178] Embodiment 21: The cartridge assembly of embodiment 1, wherein the well plate is Well transition ports arranged in a predetermined manner corresponding to the rotary valve assembly the well plate includes well ejection ports aligned with corresponding wells, The well plate is extended between the corresponding well exit port and the well transition port. The well includes an outlet channel.

[0179] Embodiment 22: The cartridge assembly of embodiment 1, wherein the well plate is A device having a top surface and a bottom surface, at least one of the surfaces including a channel, a side opening channel, the base being adapted to close the side opening channel; The layer is bonded to the

[0180] Embodiment 23: The cartridge assembly of embodiment 1, wherein the well plate is an optical interface window provided in an optical analysis station; The top surface of includes an insertion limiting element that engages with the lighting element of the instrument.

[0181] Embodiment 24: The cartridge assembly of embodiment 23, wherein the insertion limiting element corresponds to one or more ribs disposed around the periphery of the optical interface window, A Z tolerance is defined between the illumination element and the optical interface window.

[0182] Embodiment 25: In a fluidic system, a housing including an illumination chamber and a well plate. a cartridge assembly having a housing, the well plate being held within the housing. and a liquid well for receiving a desired amount of liquid, the well plate being adapted to receive the illumination channel. a fluid analysis station aligned with the chamber, the well plate being attached to the fluid analysis station. a cartridge assembly including an interface window and an interface port located in the cartridge assembly; a flow cell cartridge having a frame including an analysis circuit therein; The frame includes a flow cell window that aligns with the analysis circuit, and the frame is disposed within the analysis circuit. a flow cell cartridge including a flow cell port fluidly coupled to the active area of ​​the the housing includes a flow cell chamber that receives the flow cell cartridge; The flow cell chamber positions the flow cell cartridge in the fluid analysis station. and positioning the flow cell such that the flow cell windows and ports are aligned with the corresponding interface windows and ports. can be.

[0183] Embodiment 26: The fluidic system of embodiment 25, wherein the flow cell chamber has a side rails and end stops, at least one of which is When the flow cell window and port are in the fully loaded position, the flow cell window and port are in the corresponding interface window. and end limits for positioning the end portions at predetermined reference points so as to be aligned with the ports. do.

[0184] Embodiment 27: The fluidic system of embodiment 26, wherein the flow cell chamber is a bias arm oriented to extend along at least one of the side rails; The bias arm projects inwardly into the flow cell chamber, the bias arm A lateral bias force is applied to the flow cell cartridge to is maintained at a predetermined reference point.

[0185] Embodiment 28: The fluid system of embodiment 27, wherein the bias arm is The cell cartridge includes a latch element that is arranged to fit into a notch on the side of the cell cartridge. The latch element maintains the flow cell cartridge at the X reference point.

[0186] Embodiment 29: The fluidic system of embodiment 25, wherein the flow cell cartridge a top and bottom frame, said top frame including said flow cell window and port; The upper frame protrudes upward from the upper frame by a predetermined height to define a Z reference point. Includes ribs that determine the position of the support.

[0187] Embodiment 30: The fluidic system of embodiment 25, wherein the flow cell cartridge The gasket includes a monolithically formed elastomeric material.

[0188] Embodiment 31: The fluidic system of embodiment 25, wherein the well plate includes a valve. a pump station and an interface channel, The source channel is a first channel between the valve station and one of the interface ports. a second fluid passage between the pump station and one of the interface ports; The fluid passageway is provided.

[0189] Embodiment 32: The fluid system of embodiment 25, wherein the illumination chamber is an illumination axis extending through the interface window, the flow cell window, and an active area within the analysis circuit; The wire is oriented to extend along the

[0190] final statement Any combination of the above concepts (if these concepts are mutually inconsistent) It should be understood that combinations are contemplated as part of the inventive subject matter disclosed herein. In particular, any combination of the above-described embodiments and the subject matter recited in the claims at the end of this disclosure is contemplated. Combinations are considered part of the subject matter of the invention disclosed herein.

[0191] All publications, patents, and patent applications cited herein are hereby incorporated by reference. It can be incorporated exactly as it is.

[0192] Various aspects of the present disclosure include methods, systems, computer readable media, and / or computer It will be appreciated that aspects of the present disclosure may be embodied as a hardware program. Software embodiments (firmware, resident software, etc.) or generally referred to herein as a "circuit," "module" or "system." " Further, the disclosed method may include computer usable program code. A computer program product embodied in a computer usable storage medium It is possible to take.

[0193] Any suitable computer usable medium may be used for the software aspects of the present disclosure. The computer usable or computer readable medium may be, for example, electronic, magnetic, optical, electromagnetic, infrared or semiconductor systems, apparatus, devices or The medium may be, but is not limited to, a computer readable The active media may include transitory and / or non-transitory embodiments. More specific examples of transferable media (a non-exhaustive list) include electrical connections that include one or more wires. Continued, Diskettes, Hard Disks, and Random Access Memory of Portable Computers (RAM), Read Only Memory (ROM), Erasable Programmable ROM (EPROM or flash memory), optical fiber, portable read-only compact storage disk (CDR OM), optical storage devices, such as transmission media for maintaining the Internet or an intranet or magnetic storage device, but is not limited to these. In addition, the computer usable or computer readable medium may be a computer program that is printed on the computer. This may be, for example, a printed document, such as paper or other suitable medium. By optically reading the program, the program is electronically captured, compiled, interpreted, or The data can then be processed in an appropriate manner and then stored in the computer's memory as required. In the context of this specification, a computer usable medium or a computer The readable medium may be used by or in connection with an instruction execution system, apparatus, or device. Any medium capable of carrying, storing, transmitting or transmitting a program It can be said that:

[0194] Program code for carrying out the operations of the methods and apparatus described herein is object oriented. It can be written in a programming language (such as Java, Smalltalk, or C++). Thus, program code for carrying out the operations of the methods and apparatus described herein may be implemented using conventional procedures. type programming language (e.g., the "C" programming language or a similar programming language) ) The program code can be written in a processor, an application specific integrated circuit (ASIC), The program may be executed by a programmable instruction processor (SPI) or other program code execution entity. The program code is simply software stored in a memory (such as the computer-readable medium described above). The program code can be called a software application. A graphical user interface ("GUI") to A graphical user interface can be generated on a display device. A graphical user interface can be generated that can also provide audible functionality. However, the program code may be implemented in any processor-controlled device (e.g. For example, a computer, server, personal digital assistant, telephone, television, or processor and / or or any processor-controlled device utilizing a digital signal processor. This can be done.

[0195] The program code may be executed locally and / or remotely. The system code may be stored, for example, completely or partially in a local memory of a processor-controlled device. However, the program code may be at least partially stored remotely. The user can also download, access, and download the software to a processor-controlled device. The computer may, for example, be capable of executing the program code entirely, or may be capable of executing the program code in a non-executable manner. The program code can be executed only partially on the user's computer. at least partially located on a local computer and / or partially executed on a remote computer or stand-alone software that runs entirely on a remote computer or server. In the latter scenario, the software package can be A remote computer can be connected to the user's computer using the

[0196] The methods and apparatus described herein are applicable in both networked and non-networked environments. The communication network may be in the radio frequency domain and / or Internet Protocol It can be a cable network that operates in the (IP) domain. However, Communications networks include the Internet (also known as the World Wide Web); Intranets, local area networks (LANs) and / or wide area networks ( A communication network may also include a distributed computing network such as a WAN. The lines may include coaxial cables, copper wires, fiber optic lines and / or hybrid coaxial lines. A communications network may operate over any part of the electromagnetic spectrum and over any signalling channel. Standards (e.g., IEEE 802 family of standards, GSM / CDMA / TDMA or any wireless standard and / or I A communications network can even include a wireless portion that uses the SM band. The present invention may even include a power line portion that is carried by electrical wiring. The law and the equipment are applicable to any wireless / It can be applied to wired communication networks.

[0197] Certain aspects of the present disclosure have been described with reference to various methods and method steps. It is understood that the method steps may be implemented by program code and / or machine instructions. The program code and / or machine instructions may be used to implement the functions / operations specified in the method. This provides a means to implement

[0198] The program code may be stored in a computer readable medium, the memory being a processor. A programmable data processor that functions in a particular manner so that the program code stored in the computer readable memory and generating or transforming a product that includes instructions for implementing various aspects of the steps. can be done.

[0199] The program code is adapted to implement the various functions and operations defined in the disclosed method. The computer or other programmable data processor may be adapted to provide steps for performing the operations. The processor / computer executes a series of steps to load the program into the processing device. It can also generate a cess.

Claims

1. a cartridge assembly having a housing containing an illumination chamber and a well plate; a cartridge assembly, the well plate being retained within the housing and having a fluid well for receiving a desired amount of fluid, the well plate including a fluid analysis station aligned with the illumination chamber, the well plate including an interface window and a plurality of interface ports located at the fluid analysis station; a flow cell cartridge having a frame containing analytical circuitry therein, the frame including a flow cell window that aligns with the analytical circuitry, the frame including a flow cell port that fluidly couples to an active area within the analytical circuitry, the analytical circuitry supporting a flow of fluid across an active area that receives incoming light from an illumination source within an instrument, and detects and acquires digital images of fluorescence emitted from the fluid in association with a fluid analytical process; Equipped with the housing includes a flow cell chamber that receives the flow cell cartridge; the flow cell chamber positions the flow cell cartridge in the fluid analysis station such that the flow cell window and the flow cell port are aligned with corresponding interface windows and interface ports, respectively; Fluid systems.

2. 2. The fluid system of claim 1, wherein the flow cell chamber includes side rails and end stops, at least one of which has an end limiter that positions the flow cell cartridge at a predetermined reference point so that the flow cell windows and flow cell ports are aligned with corresponding interface windows and interface ports, respectively, when the flow cell cartridge is in a fully loaded position.

3. 3. The fluid system of claim 2, wherein the flow cell chamber includes a bias arm oriented to extend along at least one of the side rails, the bias arm protruding inwardly of the flow cell chamber, the bias arm applying a lateral bias force to the flow cell cartridge to maintain the flow cell cartridge at a predetermined reference point.

4. 4. The fluid system of claim 3, wherein the bias arm provides a lateral bias force to the flow cell cartridge to maintain the flow cell cartridge at a desired Y reference point relative to an XYZ coordinate system, and the bias arm includes a latch element configured to mate with a notch provided in a side of the flow cell cartridge, the latch element maintaining the flow cell cartridge at a desired X reference point relative to the XYZ coordinate system along a loading direction.

5. 2. The fluid system of claim 1, wherein the flow cell cartridge includes top and bottom frames, the top frame including the flow cell window and port, and the top frame including a rib protruding upwardly from the top frame a predetermined height to define a Z reference point with respect to an XYZ coordinate system.

6. The fluid system of claim 1 , wherein the flow cell cartridge includes a gasket monolithically formed from an elastomeric material.

7. 2. The fluid system of claim 1, wherein the well plate includes a valve station, a pump station, and an interface channel, the interface channel providing a first fluid passage between the valve station and one of the interface ports and a second fluid passage between the pump station and one of the interface ports.

8. The fluid system of claim 1 , wherein the illumination chamber is oriented to extend along an illumination axis that extends through the interface window, the flow cell window, and an active area in the analysis circuit.

Images