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WO2003100380A2 - Plate-forme monobloc de traitement d'echantillons - Google Patents

Plate-forme monobloc de traitement d'echantillons Download PDF

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Publication number
WO2003100380A2
WO2003100380A2 PCT/US2003/016905 US0316905W WO03100380A2 WO 2003100380 A2 WO2003100380 A2 WO 2003100380A2 US 0316905 W US0316905 W US 0316905W WO 03100380 A2 WO03100380 A2 WO 03100380A2
Authority
WO
WIPO (PCT)
Prior art keywords
biochip
platform
analytic device
desktop analytic
desktop
Prior art date
Application number
PCT/US2003/016905
Other languages
English (en)
Other versions
WO2003100380A3 (fr
Inventor
Fareed Kureshy
Vijay Mahant
Shailendra Singh
Original Assignee
Autogenomics, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from PCT/US2002/017006 external-priority patent/WO2003102241A1/fr
Application filed by Autogenomics, Inc. filed Critical Autogenomics, Inc.
Priority to AU2003237283A priority Critical patent/AU2003237283A1/en
Priority to US10/513,459 priority patent/US7776195B2/en
Priority to JP2004507791A priority patent/JP2006510872A/ja
Priority to EP03736749A priority patent/EP1508028A4/fr
Publication of WO2003100380A2 publication Critical patent/WO2003100380A2/fr
Publication of WO2003100380A3 publication Critical patent/WO2003100380A3/fr

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00584—Control arrangements for automatic analysers
    • G01N35/00722—Communications; Identification
    • G01N35/00732—Identification of carriers, materials or components in automatic analysers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00029—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
    • G01N35/1016—Control of the volume dispensed or introduced
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00029—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides
    • G01N2035/00099—Characterised by type of test elements
    • G01N2035/00158—Elements containing microarrays, i.e. "biochip"
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00584—Control arrangements for automatic analysers
    • G01N35/00594—Quality control, including calibration or testing of components of the analyser
    • G01N35/00613—Quality control
    • G01N35/00663—Quality control of consumables
    • G01N2035/00673—Quality control of consumables of reagents
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00584—Control arrangements for automatic analysers
    • G01N35/00722—Communications; Identification
    • G01N35/00732—Identification of carriers, materials or components in automatic analysers
    • G01N2035/00742—Type of codes
    • G01N2035/00782—Type of codes reprogrammmable code
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
    • G01N2035/1025—Fluid level sensing

Definitions

  • the field of the invention is automated desktop analytic devices, especially for use in high-throughput screening.
  • binding of an analyte is electronically detected, (e.g.,
  • Nanogen's Nanochip® various steps, including capture probe loading, analyte binding, and washing of the chip are performed in one station (e.g., Nanochip® Loader), while binding analysis is performed in a separate detector station (e.g., Nanochip® Reader).
  • a separate detector station e.g., Nanochip® Reader
  • Electronic detection often allows multiple reuse of a biochip, and typically exhibits significantly accelerated analyte binding.
  • the operator must manually transfer the chip from one station to the other, requiring proper insertion and operator control to commence detection, which at least somewhat defies the concept of automated high-throughput analysis.
  • biochips are commercially available as arrays of capture probes disposed on a microscope glass slide. Detection of labeled analytes that are bound to the capture probes is then performed with a flatbed scanner that typically acquires fluorescence data from the array on the surface of the slide. High-throughput analysis of such arrays is often relatively inexpensive.
  • binding of the analyte may be optically detected in a chip that is disposed in a housing (e.g., Genechip by Affymetrix).
  • a housing advantageously protects the biochip from inadvertent damage, and may further control flow of fluids (e.g. , volume and/or flow control).
  • fluids e.g. , volume and/or flow control
  • such systems generally require processing the chip in a fluidics/hybridization station for binding and washing of an analyte that is bound to the capture probes, while analyte binding is detected in a separate detector. Again, an operator needs to manually insert the chip into the detector and select the suitable detection protocol prior to analysis.
  • detection of the signal typically requires that fluids be completely removed from the chip to prevent quenching of the signal or other undesirable optical effects.
  • multi-well plates may be used in a robotic station that automatically transfers a multi-well plate from a fluidics station to a plate reader station (see e.g., robotic stations from Beckman, Hudson, Hamilton, Gilson, Perkin Elmer, or Quiagen).
  • robotic stations often integrate fluidics and detection, and employ relatively inexpensive multi-well plates.
  • customization of multi-well plates is generally relatively simple and can often be done using the same robotic station.
  • robotic stations for multi-well plates generally have a relatively large footprint, especially where several thousand samples per day are processed. Smaller modular systems are also commercially available, however, typically fail to provide integrated sample analysis.
  • detection of analytes in multi-well based systems is generally limited to microplate readers, which often provide limited accuracy and only perform well in assays where optical detection is not critically impaired by variations in focal depth.
  • the present invention is directed to an desktop analytic device for a biochip, wherein fluidics management and confocal microscope signal detection are integrated using a sample processing platform, wherein the platform serves as a basis for fluidics management, and wherein the biochip is moved along the x- and/or y-coordinate from the platform to the detector without manual user intervention.
  • the desktop analytic device includes a substantially horizontal sample processing platform that receives a biochip that is at least partially enclosed in a housing, wherein the biochip is at least partially immersed by a fluid that is retained by the housing, wherein the biochip binds an analyte from the fluid, and wherein the fluid further comprises a non-analyte.
  • An energy source e.g., heater, cooling element, or ultrasound source
  • a confocal microscope detector is coupled to the platform such that a substantially horizontal transport path is formed between the detector and the platform, wherein the biochip is moved in a sliding motion from the platform to the detector using the transport path.
  • the biochip is moved within the desktop analytic device without manual intervention of an operator from the platform to the detector while the analyte is bound to the biochip, and that the sample processing platform and the detector are enclosed in the desktop analytic device.
  • movement of the biochip from the platform to the detector is caused by an actuator that pushes the biochip along at least one of an x- coordinate and a y-coordinate, and it is still further preferred that the biochip is further transported from a multi-biochip magazine to the sample processing platform within the desktop analytic device and without manual intervention of an operator (movement of the biochip from the multi-biochip magazine to the platform is preferably caused by the same actuator).
  • contemplated sample processing platform may be configured to receive a second biochip, wherein the biochip is moved from the platform to the detector while the biochip is at least partially immersed in a second fluid.
  • a data transfer interface may further be coupled to the device and couples the desktop analytic device with a person other than the operator of the desktop analytic device (e.g., in a remote location relative to the desktop analytic device).
  • contemplated desktop analytic devices may comprise a multi-biochip magazine, a fluidics station with a stringency platform, and confocal microscope detector, wherein a biochip is moved from the magazine via the stringency platform to the detector without manual intervention of an operator.
  • the multi-biochip magazine and/or the stringency platform move along a x-coordinate (e.g., via stepper motor, piezo motor, or linear motor) while the biochip is moved along a y-coordinate (e.g. , via actuator).
  • the fluidics station in still further contemplated devices will include automatic pipette disposed within the device, wherein the pipette moves along at least one of an x- coordinate, a y-coordinate, and a z-coordinate.
  • the biochip is moved while the biochip is at least partially immersed in a fluid, and that the stringency platform, the multi-biochip magazine, and/or the confocal microscope detector are coupled to each other such that a portion of the stringency platform and a portion of the confocal microscope detector or multi-biochip magazine abut each other to form a transport path.
  • Figure 1 is a schematic view of an exemplary analytic device according to the inventive subj ect matter.
  • Figure 2 is a schematic view of an exemplary sample processing platform that is coupled to a confocal microscope detector according to the inventive subject matter.
  • the term "desktop analytic device” refers to an integrated apparatus in which a housing at least partially, and more typically entirely encloses at least a detector and a fluidics station, and wherein the apparatus is portable as a single piece of equipment from one location to another location. Particularly preferred dimensions for contemplated desktop analytic devices will allow placement of the device on top of a standard sized laboratory bench.
  • a device that includes within a housing (e.g., 40 inches width x 30 inches depth x 20 inches height) a detector, a fluidics station, a sample holder (e.g., a multi-well plate), a multi-biochip magazine, and a multi- reagent pack is considered a desktop analytic device under the scope of this definition, while an assembly of a robotic arm, a fluidics station, and a multi-well plate reader on a mounting platform is not considered a desktop analytic device under the scope of this definition.
  • the term "fluidics station” refers to a subsystem of an analytic device, wherein the subsystem is configured to receive (and preferably retain) a biochip, and wherein a fluid dispensing mechanism (e.g., automated pipette, tubing, etc) provides and/or removes fluid to and/or from the biochip while the biochip is disposed on a platform.
  • a fluid dispensing mechanism e.g., automated pipette, tubing, etc
  • Particularly preferred platforms generally include a flat surface, optionally comprising a retaining and/or guiding structure for the biochip, wherein the term “substantially horizontal” means that the platform forms an angle with an absolute horizontal of no more than 15 degrees.
  • biochip generally refers to a carrier that has a plurality of probes (to which an analyte may be coupled) in predetermined positions.
  • at least one of the probes is coupled to the carrier via a crosslinker that is disposed in a matrix
  • exemplary multi-substrate biochips are described in commonly-owned and copending U.S. Patent Application No. 10/346,879, filed January 17, 2003, and the PCT applications with the serial numbers PCT US02/03917, filed January 24, 2002, and PCT/US01/47991, filed December 11, 2001, all of which are incorporated by reference herein.
  • the term “biochip” and "biochip-containing device” specifically excludes a multi-well plate.
  • predetermined position of an analyte refers to a particular position of the analyte on the chip that is addressable by at least two coordinates relative to a registration marker on the chip, and particularly excludes a substantially complete coating of the chip with the analyte an/or probe. Therefore, preferred pluralities of predetermined positions will include an array with a multiple rows of substrates forming multiple columns.
  • registration marker refers to a marker on the biochip that is used to provide a reference point for a position of an analyte.
  • the registration marker is optically detectable and comprises a fluorescent dye, a luminescent, light-absorbing, and/or light-reflective compound, wherein illumination of the registration marker is most preferably performed at a wavelength that is not absorbed by the label of the analyte.
  • the term "probe” generally refers to any molecule, complex of molecules, or cell that binds to an analyte with a dissociation constant K D ⁇ 10 "2 M, and more typically K D ⁇ 10 "3 M, at a temperature of 25°C and physiological buffer conditions (e.g., pH between 6.5 and 8.5, and ionic strength sufficient to maintain native conformation, viability, and/or Watson-Crick hybridization (between ligand and anti-ligand) of the anti-ligand).
  • a dissociation constant K D ⁇ 10 "2 M and more typically K D ⁇ 10 "3 M
  • physiological buffer conditions e.g., pH between 6.5 and 8.5, and ionic strength sufficient to maintain native conformation, viability, and/or Watson-Crick hybridization (between ligand and anti-ligand) of the anti-ligand.
  • suitable probes include nucleic acids (and their analogs), polypeptides, lipids, macromolecular complexes of nucleic acids, polypeptides, carbohydrates, and lipids, as well as viruses, bacteria and/or eukaryotic cells.
  • the probe may further include a label.
  • a probe on the biochip may include a fluorescent label, wherein the fluorescence is quenched by a molecule that binds to the probe.
  • a probe may also include an optically detectable label (e.g. , for calibration of a signal in a quantitative assay).
  • analyte refers to any molecule, complex of molecules, or cell that binds to the probe with a dissociation constant of K D ⁇ 10 "2 M and more typically K D ⁇ 10 "3 M, at a temperature of 25°C and physiological buffer conditions (i.e., pH between 6.5 and 8.5, and ionic strength sufficient to maintain native conformation, viability, and/or Watson-Crick hybridization (between ligand and anti- ligand) of the anti-ligand).
  • physiological buffer conditions i.e., pH between 6.5 and 8.5, and ionic strength sufficient to maintain native conformation, viability, and/or Watson-Crick hybridization (between ligand and anti- ligand) of the anti-ligand.
  • suitable analytes include nucleic acids (and their analogs), polypeptides, lipids, metabolites, hormones, macromolecular complexes of nucleic acids, polypeptides, carbohydrates, and lipids, as well as viruses, bacteria and/or eukaryotic cells.
  • the analyte may include an optically detectable label, which may be naturally present in the analyte, or coupled to the analyte before, during or after binding of the analyte to the probe.
  • Particularly contemplated labels include light-absorbing compounds, fluorescent labels, phosphorescent labels, and luminescent labels that produce an analyte signal where the label is coupled to the analyte.
  • Contemplated analyte signals therefore include a fluorescence signal, a chemiluminescence signal, or a phosphorescence signal.
  • a probe and an analyte form an optically detectable binding pair, wherein the analyte is optically detected via the label.
  • biochip is moved/transported "without manual intervention of an operator" means that actuation of the biochip occurs without the operator physically touching (e.g., manually gripping or lifting) the biochip, however, does not exclude manual programming (e.g., typing on a keyboard or touch screen) of the analytic device to effect automatic movement of the biochip.
  • an exemplary desktop analytic device 100 includes a housing 110 that encloses a confocal microscope detector 120 that is coupled to a sample processing platform 160 via pathway 162.
  • the sample processing platform 160 includes an energy source (e.g., Peltier element, not shown), and abuttingly coupled to the sample processing platform 160 is multi-biochip magazine 140 that provides one or more biochips (not shown) to the platform 160.
  • the biochips are moved from the magazine to the platform, and from the platform to the detector via actuator 150, wherein the robotic arm that includes the actuator 150 further includes an automatic pipette (not shown).
  • Sample station 170 includes multi-well plates from which the automatic pipette transfers sample fluid to the biochip.
  • Multi-reagent packs 130 provide the required reagents for reaction and other processing steps of the sample in the biochip.
  • a data transfer interface 180 provides data connectivity to a computer located outside of the housing 110. Therefore, in an especially preferred aspect of contemplated desktop analytic devices, a sample processing platform is operationally coupled to at least a confocal microscope detector and a biochip magazine as schematically depicted in exemplary configuration 200 of Figure 2.
  • the confocal microscope detector 220 is abuttingly coupled to the sample processing platform 260 (which is coupled to Peltier element 262) to form substantially horizontal transport path 222 for the biochip-containing device 242.
  • Biochip-containing device 242 includes biochip 242A that is coupled to housing 242A', wherein housing 242A' retains fluid 242D from which analyte 242C is bound to probe 242B (which is coupled to the biochip).
  • Actuator 250 comprises manipulator arm 254 (which is most preferably movable coupled to the actuator, wherein the arm may be rotated about its longitudinal axis and/or extended from the actuator 250) and automatic pipette 252.
  • actuator 250 or manipulator arm 254 descends to the biochip-containing device 242 and pushes the device into a suitable opening of the detector 220 (see actuator in dotted lines and dotted opening).
  • additional actuator mechanism 290A may move the sample processing platform along at least one coordinate (preferably along a coordinate other than the movement of the device 242).
  • Multi-biochip magazine 240 provides a plurality of additional devices 244 to the analyzer, wherein the actuator 250 (or manipulator arm 254) pushes the device 244 from one side of the magazine to the platform as indicated by the dotted rendition of the actuator to the right of the magazine.
  • the actuator 250 or manipulator arm 254 pushes the device 244 from one side of the magazine to the platform as indicated by the dotted rendition of the actuator to the right of the magazine.
  • multiple devices 242 may be present on the platform 260.
  • the magazine may be translated along at least one coordinate using magazine actuator mechanism 290B (and preferably along a coordinate other than the movement of the device 242).
  • a separate transfer path e.g., small non- movable platform abuttingly coupled to both the platform and the magazine
  • a separate transfer path e.g., small non-movable platform abuttingly coupled to both the platform and the detector
  • Sample fluid may be provided from a multi-well plate 270, which may also be movable in the analytic device via actuator mechanism 290C and/or reagents may be provided from a multi-reagent pack (not shown), which may also be movable in the analytic device via actuator mechanism 290C. Removal and/or transfer of fluids and/or reagents to and from the device 242 is preferably performed using the automatic pipette 252.
  • the detector comprises a confocal and/or dark field microscope, and particularly suitable detectors are described in our commonly owned and copending application with the title “Microarray Detector and Methods", filed on May 28, 2003, which is incorporated by reference herein.
  • optical detectors are also suitable for use herein so long as a biochip can be moved along a substantially horizontal transport path between the platform and the detector. It is further contemplated that suitable detectors may have an opening that can be sealed to prevent stray light from interfering with a test performed in the detector. Such sealing is preferably achieved with a slidable or otherwise moving door, but is not necessarily limiting to the inventive concept presented herein.
  • the detector temporarily or permanently forms a substantially horizontal transport path with the platform by abutting with at least part of the platform.
  • the platform may be moved towards the detector to abut with the detector, thereby forming a transport path for the biochip.
  • a separate substantially horizontal intermediate platform may be included wherein the intermediate platform is (at least temporarily) coupled to the detector and/or the sample processing platform.
  • the biochip is preferably retained (relative to at least one coordinate) in the detector via a retaining mechanism, and a particularly preferred retaining mechanism includes a guide rail that engages one (and more typically two sides) of a biochip (or a housing of the biochip).
  • biochips are those that comprise a plurality of probes (to which an analyte may be coupled) in predetermined positions.
  • at least one of the probes is coupled to the carrier via a crosslinker that is disposed in a matrix
  • exemplary multi-substrate biochips are described in commonly- owned and copending U.S. Patent Application No. 10/346,879, filed January 17, 2003, and PCT application with the serial number PCT/US02/03917, filed January 24, 2002.
  • the biochip is disposed in a housing and exemplary biochip-containing devices are described in our commonly owned copending PCT application with the serial number PCT/US01/47991, which was filed December 11, 2001.
  • the housing of the biochip includes a base that is thermally conductive (e.g., metal base, or includes metal filings in a polymeric base).
  • contemplated biochips and/or biochip-containing devices may be modified and all of such alternative biochips are deemed suitable for use herein.
  • the housing may include a movable cover, various fluid channels for addition and/or removal of fluids, optical implements, and/or other elements that will directly or indirectly interact with the fluid, analyte, and/or probe.
  • the biochip may include a base or other element that engages with a biochip guiding structure in the platform and/or detector.
  • suitable biochips will generally include a plurality (e.g., between 25 and several hundred) of probes in predetermined positions, wherein one or more of the probes may bind an analyte from a sample fluid (e.g., biological fluid of a patient) comprising a plurality of non-analytes. Consequently, the biochip will be at least in part immersed in a fluid (e.g. , sample fluid, hybridization or binding buffer, or wash fluid, preferably retained by the housing of the biochip) while the biochip is in the detector and/or in the sample processing platform, or while the biochip is moved from the sample processing platform to the detector.
  • a fluid e.g. , sample fluid, hybridization or binding buffer, or wash fluid, preferably retained by the housing of the biochip
  • the biochips may be disposed in a multi-biochip magazine, wherein the magazine is coupled to the sample processing platform.
  • the magazine may be directly and abuttingly coupled to the platform to form a substantially horizontal transfer path.
  • a separate horizontal transfer path may be coupled to the magazine and the platform to ensure sliding transfer or other movement between the magazine and the platform.
  • an actuator infra moves the biochip from the magazine to the platform.
  • the platform is configured such that the platform receives and at least temporarily retains a biochip from a location other than the platform. Consequently, suitable platforms will have a size that corresponds to at least the size of the biochip, and more typically to a multiple of the size of a biochip to accommodate more than one biochip at a time (e.g., where multiple samples are incubated at the same time before analysis). Furthermore, it is generally preferred that the platform has a guiding structure that provides guided movement of the biochip when the biochip is pushed by an actuator from one position to another position.
  • a suitable guiding structure may include an engaging rail along which the base of the biochip moves.
  • the platform may also include a channel in which the biochip can move along one or two coordinates (i.e., x- and y-coordinate).
  • the platform may be in a fixed position or movable coupled to the housing.
  • the actuator and/or platform is configured to enable movement of the biochip along x- and y-coordinate
  • the platform may be in a fixed position.
  • the platform is movably coupled relative to the detector.
  • a motor e.g., stepper, piezo, linear, or other electromotor
  • Contemplated sample processing platforms are generally substantially horizontal and are functionally coupled to an energy source that provides energy to the fluid in the biochip.
  • the energy source may advantageously include a heater and/or a cooling element, which may be separately coupled to the platform or combined (e.g., as a Peltier element).
  • an ultrasound transducer may provide ultrasound energy to disrupt such non-specific binding.
  • Further contemplated energy sources include light energy sources (e.g., to destroy a photolabile compound), radiation energy sources, and all reasonable combinations thereof.
  • the energy source will typically depend at least in part on the particular energy source.
  • the energy source is a heater and/or cooler
  • physical coupling to the platform is generally preferred.
  • indirect coupling may be suitable by directing a beam of radiation to the fluid and/or biochip.
  • the transducer may be coupled to the platform or may be inserted (e.g., via a transducer tip) into the fluid (e.g., using the actuator).
  • Appropriate energy levels will generally depend on the nature of the energy source, and it is contemplated that suitable energy levels will be in the range of several mW to several W (e.g. , to create a photoradical, or to heat the fluid from 25 centigrade to 45 centigrade).
  • Particularly preferred actuators in contemplated desktop analytic devices comprise a robotic arm that moves along one coordinate (e.g., x-coordinate) and that further includes an additional functional element that moves along at least one other coordinate (e.g., y- 5 and/or z-coordinate).
  • preferred actuators may include a manipulator arm which may be moved in a rotational and/or translational (e.g., front-to- back, or side-to-side) movement. Such movement may be employed to impart a sliding movement to the biochip that may be disposed on the sample processing platform (e.g., to move the biochip from the platform to the detector via the transfer path, or to move the biochip from the magazine to the platform via another transfer path).
  • movement of the biochip from the platform to the detector may be caused by an actuator that pushes the biochip along at least one of an x-coordinate and a y- coordinate.
  • Actuator-based movement of the biochip may further be employed to move the biochip among numerous alternative locations within the desktop analytic device, and particularly contemplated alternative movements include sliding movements from a multi-biochip magazine to the sample processing platform (using the same of a different actuator without manual operation intervention).
  • actuators will also include an automatic pipette that transfers liquid from one location to another (e.g., from a multi-reagent pack to the biochip, or from a sample reservoir to the biochip) within the desktop analytic device.
  • the actuator may have various alternative configurations so long as the actuator still provides movement (most preferably sliding movement) to the biochip.
  • suitable actuators may include those in which a robotic arm moves along two coordinates (e.g., x-, and y-coordinate) and that further includes an additional functional element that moves along at least one other coordinate (e.g., y-, and/or z-coordinate).
  • the actuator may also include a robotic arm that moves along three coordinates in translational and/or rotational motion. Less preferred (but not excluded) actuators will include actuators that lift the biochip from a first position to a second position.
  • the biochip is moved within contemplated desktop analytic devices without manual intervention of an operator from a first location to a second location, and more preferably from the sample processing platform (fluidics station) to the detector while one or more analytes are bound to the biochip.
  • another structure e.g. , the platform and/or the detector
  • the biochip is moved within contemplated desktop analytic devices without manual intervention of an operator from a first location to a second location, and more preferably from the sample processing platform (fluidics station) to the detector while one or more analytes are bound to the biochip.
  • Contemplated desktop analytic devices may advantageously include a data transfer interface that is electronically coupled to one or more components of the analytic device, and especially contemplated components include a computer that controls operation of the analytic device (and may further provide test data analysis), the detector, and the sample processing platform.
  • Such data transfer interfaces e.g., telephonic, DSL, or cable modem
  • the sample processing platform may include various sensors that provide feedback on operating condition, number of biochips, environmental parameters, etc.
  • a status code e.g., incubation in progress, over-temperature alarm, etc.
  • a status code e.g., incubation in progress, over-temperature alarm, etc.
  • a person other than the operator may be in a remote location relative to the analytic device (e.g., at a different ZIP code, different city, county, or even state).
  • the inventors particularly contemplate a desktop analytic device having a substantially horizontal sample processing platform that receives a biochip that is at least partially enclosed in a housing, wherein the biochip is at least partially immersed by a fluid that is retained by the housing, wherein the biochip binds an analyte from the fluid, and wherein the fluid further comprises a non-analyte.
  • An energy source is functionally coupled to the platform and delivers energy to the fluid in the biochip
  • confocal microscope detector is coupled to the platform such that a substantially horizontal transport path is formed between the detector and the platform, wherein the biochip is moved in a sliding motion from the platform to the detector via the transport path.
  • the biochip is moved within the desktop analytic device without manual intervention of an operator from the platform to the detector while the analyte is bound to the biochip, wherein the sample processing platform and the detector are enclosed in the desktop analytic device.
  • contemplated desktop analytic devices include a multi-biochip magazine, a fluidics station with a sample processing platform, and confocal microscope detector, wherein a biochip is moved from the magazine via the sample processing platform to the detector without manual intervention of an operator.
  • At least one of the multi-biochip magazine and the stringency platform move along a x- coordinate while the biochip is moved along a y-coordinate
  • the fluidics station comprises an automatic pipette disposed within the device, wherein the pipette moves along at least one of an x-coordinate, a y-coordinate, and a z-coordinate.
  • the multi-biochip magazine and/or the stringency platform are actuated by a stepper motor, piezo motor, or a linear motor, wherein the biochip is actuated by an actuator that pushes the biochip along at least one of an x-coordinate and a y-coordinate (preferably, the biochip is moved while the biochip is at least partially immersed in a fluid).
  • the stringency platform and the confocal microscope detector are coupled to each other such that a portion of the stringency platform and a portion of the confocal microscope detector abut each other to form a transport path.
  • the stringency platform and the multi-biochip magazine may be coupled to each other such that a portion of the stringency platform and a portion of the multi- biochip magazine abut each other to form another transport path.
  • analytic devices may further include a multi-reagent pack and an automated pipettor to form an integrated analytic device.
  • Particularly preferred automatic pipettors contemplated in conjunction with the teachings presented herein include those described in our co-pending international patent application with the title “Level-Controlled Pipette For Automated Analytic Devices", filed May, 28, 2003, which is incorporated by reference herein.
  • Particularly preferred multi-reagent packs contemplated in conjunction with the teachings presented herein include those described in our co-pending international patent application with the title “Multi-Reagent Pack", filed May, 28, 2003, which is incorporated by reference herein.

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  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)

Abstract

L'invention concerne un dispositif analytique monobloc de bureau comprenant une station fluidique couplée à un détecteur de microscope confocal, ainsi qu'une puce à ADN déplacée de la station fluidique vers le détecteur sans intervention manuelle d'un utilisateur.
PCT/US2003/016905 2002-05-28 2003-05-28 Plate-forme monobloc de traitement d'echantillons WO2003100380A2 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
AU2003237283A AU2003237283A1 (en) 2002-05-28 2003-05-28 Integrated sample processing platform
US10/513,459 US7776195B2 (en) 2002-05-28 2003-05-28 Integrated sample processing platform
JP2004507791A JP2006510872A (ja) 2002-05-28 2003-05-28 統合された試料処理プラットフォーム
EP03736749A EP1508028A4 (fr) 2002-05-28 2003-05-28 Plate-forme monobloc de traitement d'echantillons

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US38389602P 2002-05-28 2002-05-28
US60/383,896 2002-05-28
USPCT/US02/17006 2002-05-29
PCT/US2002/017006 WO2003102241A1 (fr) 2002-05-29 2002-05-29 Système de micro-réseau intégré et procédés associés

Publications (2)

Publication Number Publication Date
WO2003100380A2 true WO2003100380A2 (fr) 2003-12-04
WO2003100380A3 WO2003100380A3 (fr) 2004-08-12

Family

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Family Applications (2)

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PCT/US2003/017073 WO2003100474A2 (fr) 2002-05-28 2003-05-28 Detecteur de microreseaux et procedes associes
PCT/US2003/016905 WO2003100380A2 (fr) 2002-05-28 2003-05-28 Plate-forme monobloc de traitement d'echantillons

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PCT/US2003/017073 WO2003100474A2 (fr) 2002-05-28 2003-05-28 Detecteur de microreseaux et procedes associes

Country Status (2)

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EP (4) EP1508027A4 (fr)
WO (2) WO2003100474A2 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110456094A (zh) * 2018-05-08 2019-11-15 赛多利斯百得液体处理公司 液体处理系统和用于分析吸头状态的方法

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20060085754A (ko) * 2005-01-25 2006-07-28 삼성전자주식회사 광학적 스캐너를 보정하기 위한 장치, 그를 제조하는 방법및 그를 이용하여 광학적 스캐너를 보정하는 방법
CA2603759A1 (fr) * 2005-04-12 2006-11-02 Caliper Life Sciences, Inc. Systeme optique compact de detection pour dispositifs de microfluidique
US8351026B2 (en) * 2005-04-22 2013-01-08 Affymetrix, Inc. Methods and devices for reading microarrays
JP2006337245A (ja) * 2005-06-03 2006-12-14 Matsushita Electric Ind Co Ltd 蛍光読み取り装置
CN102622746B (zh) 2005-09-21 2016-05-25 卢米尼克斯股份有限公司 图像数据处理的方法和系统
JP4711125B2 (ja) * 2005-09-27 2011-06-29 横河電機株式会社 バイオチップ、バイオチップ読み取り装置、およびバイオチップ読み取り方法
JP4955244B2 (ja) * 2005-09-27 2012-06-20 横河電機株式会社 バイオチップ読み取り装置およびバイオチップ読み取り方法
US11035823B2 (en) 2009-03-17 2021-06-15 Qiagen Sciences, Llc Methods and devices for sequencing nucleic acids in smaller batches
US8481259B2 (en) 2007-02-05 2013-07-09 Intelligent Bio-Systems, Inc. Methods and devices for sequencing nucleic acids in smaller batches
CA2677216C (fr) 2007-02-05 2015-10-20 Intelligent Bio-Systems, Inc. Dispositif de detection et procedes d'utilisation
US11940413B2 (en) 2007-02-05 2024-03-26 IsoPlexis Corporation Methods and devices for sequencing nucleic acids in smaller batches
JP5072688B2 (ja) 2008-04-02 2012-11-14 キヤノン株式会社 走査型撮像装置
US9767342B2 (en) 2009-05-22 2017-09-19 Affymetrix, Inc. Methods and devices for reading microarrays
KR101979287B1 (ko) 2011-10-18 2019-08-28 루미넥스 코포레이션 이미지 데이터를 처리하기 위한 방법 및 시스템

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000066269A1 (fr) 1999-05-03 2000-11-09 Ljl Biosystems, Inc. Systeme integre de traitement d'echantillons
US6150173A (en) 1996-05-29 2000-11-21 Schubert; Walter Automated determining and measuring device and method
US6207031B1 (en) 1997-09-15 2001-03-27 Whitehead Institute For Biomedical Research Methods and apparatus for processing a sample of biomolecular analyte using a microfabricated device

Family Cites Families (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4975647A (en) * 1987-06-01 1990-12-04 Nova Biomedical Corporation Controlling machine operation with respect to consumable accessory units
GB8816982D0 (en) * 1988-07-16 1988-08-17 Probus Biomedical Ltd Bio-fluid assay apparatus
GB9125603D0 (en) * 1991-12-02 1992-01-29 Gec-Marconi Limited Optical analysis system and positioning apparatus therefor
CA2512707C (fr) * 1992-03-27 2009-05-12 Abbott Laboratories Fermeture automatique de recipients
DE4326342A1 (de) * 1993-08-05 1995-02-09 Boehringer Mannheim Gmbh Verfahren zur Analyse von Probenflüssigkeiten
US5582798A (en) * 1995-02-23 1996-12-10 Cyberlab Inc. Volume sensing device
US5741462A (en) * 1995-04-25 1998-04-21 Irori Remotely programmable matrices with memories
US6329139B1 (en) * 1995-04-25 2001-12-11 Discovery Partners International Automated sorting system for matrices with memory
JP4663824B2 (ja) * 1996-12-31 2011-04-06 ハイ スループット ジェノミクス インコーポレイテッド 多重化分子分析装置および方法
AU748939B2 (en) * 1997-02-20 2002-06-13 Regents Of The University Of California, The Plasmon resonant particles, methods and apparatus
WO1999005308A2 (fr) * 1997-07-22 1999-02-04 Rapigene, Inc. Appareil et procedes pour realiser une dispersion matricielle d'une solution sur un support solide
US6257091B1 (en) * 1998-07-14 2001-07-10 Bayer Corporation Automatic decapper
FR2786876B1 (fr) * 1998-12-03 2001-08-31 Nicolas Bara Enceinte refrigeree pour le stockage d'articles pourvue de moyens de controle du contenu de l'enceinte
JP4608043B2 (ja) * 1999-09-24 2011-01-05 オリンパス株式会社 顕微鏡用焦点検出装置
US6362004B1 (en) * 1999-11-09 2002-03-26 Packard Biochip Technologies, Llc Apparatus and method for using fiducial marks on a microarray substrate
JP3736278B2 (ja) * 2000-04-12 2006-01-18 松下電器産業株式会社 生化学物質の観察方法

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6150173A (en) 1996-05-29 2000-11-21 Schubert; Walter Automated determining and measuring device and method
US6207031B1 (en) 1997-09-15 2001-03-27 Whitehead Institute For Biomedical Research Methods and apparatus for processing a sample of biomolecular analyte using a microfabricated device
WO2000066269A1 (fr) 1999-05-03 2000-11-09 Ljl Biosystems, Inc. Systeme integre de traitement d'echantillons

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP1508028A4

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110456094A (zh) * 2018-05-08 2019-11-15 赛多利斯百得液体处理公司 液体处理系统和用于分析吸头状态的方法

Also Published As

Publication number Publication date
WO2003100474A2 (fr) 2003-12-04
EP1508048A1 (fr) 2005-02-23
EP1508027A2 (fr) 2005-02-23
EP1508029A4 (fr) 2010-04-14
WO2003100380A3 (fr) 2004-08-12
EP1508048A4 (fr) 2009-11-04
EP1508027A4 (fr) 2009-04-22
EP1508028A4 (fr) 2009-05-20
WO2003100474A3 (fr) 2004-10-21
EP1508029A1 (fr) 2005-02-23
EP1508028A2 (fr) 2005-02-23

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