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
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N1/00—Sampling; Preparing specimens for investigation
  • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
  • G01N1/30—Staining; Impregnating ; Fixation; Dehydration; Multistep processes for preparing samples of tissue, cell or nucleic acid material and the like for analysis
  • G01N1/31—Apparatus therefor
  • G01N1/312—Apparatus therefor for samples mounted on planar substrates
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
  • B01J2219/00277—Apparatus
  • B01J2219/00497—Features relating to the solid phase supports
  • B01J2219/00527—Sheets
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
  • B01J2219/00583—Features relative to the processes being carried out
  • B01J2219/00596—Solid-phase processes
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
  • B01J2219/00583—Features relative to the processes being carried out
  • B01J2219/00603—Making arrays on substantially continuous surfaces
  • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
  • B01J2219/00583—Features relative to the processes being carried out
  • B01J2219/00603—Making arrays on substantially continuous surfaces
  • B01J2219/00659—Two-dimensional arrays
• • 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"

Definitions

• Biochips allow a very large number of molecules to be analyzed in parallel. They are mainly nucleic acids and proteins.
• the basic principle is the recognition and pairing of two molecules, which have affinities.
• One of the collections of molecules is fixed, in the form of mini or microdeposits, on a solid support, fabric, glass slide, silicon chip ...
• the other molecule which is labeled, generally in solution, is brought into contact with the samples deposited on the solid support. After an incubation time, the excess of labeled molecule is eliminated and the support is washed thoroughly. It is then a question of detecting and quantifying the signal emitted by the molecules retained on the deposits. In some cases, the retained molecule can be "dropped" from the deposits and a new molecule can be tested with the same solid support.
• biochips Generally, to treat biochips, put the deposits in contact with different reagents and then wash them thoroughly. The temperature of the reagents and biochips must be adjusted. The markers are most often fluorescent, but other labeling techniques can be used.
• the labeled molecule is a rare and / or expensive element.
• the volume required should be minimized.
• the other reagents, and in particular the detergents, are inexpensive and the reduction in the volumes used is much less.
• the invention relates to an automaton capable of carrying out, without human intervention, the processing of biochips and the acquisition of signals for their analysis. In addition to saving reagents, the automated system can process a large number of biochips. Its simplicity makes it relatively inexpensive equipment.
• the heart of the device is a battery of reactors which are described below.
• the device cover has different elements:
• a number of regularly spaced fixed nozzles equal to the number of reactors and located so as to dispense liquid therein. These nozzles are connected by calibrated catheters to the cover of an airtight enclosure which comprises a number of tubes containing the labeled molecules.
• This enclosure can be put under a given pressure for a given time, thanks to a gas cylinder, for example, which has the effect of driving back by the catheters to the reactors the same volume of the liquids contained in the tubes.
• This enclosure can be cooled by any method to ensure good conservation of the labeled molecules.
• a number of nozzles fixed on the cover between the previous ones connected to pressure or vacuum bottles, or to pumps, allows the common reagents to be distributed in large volumes (a few milliliters) to each reactor. Some of these nozzles can spray liquids for cleaning and decontaminating the device.
• a mechanical translation device makes it possible to move apart, then to return to its initial position, a sliding piece supporting biochips of each reactor or in other cases the reactors, themselves, successively.
• the temperature inside the enclosure containing the reactors is regulated.
• the movable strip has a thermostat element, for heating and / or cooling the biochip.
• These heating or cooling elements are constituted by a PELTIER effect element.
• They can also be produced by conduits for the circulation of heat transfer fluids, making it possible to adjust the temperature cycles between 97 ° C and 50 ° C, with cyclic temperature changes.
• Thermoregulation can also be achieved by a two-phase capillary pumping loop. If necessary, the humidity of the air in the enclosure can be checked.
• Figures 1, 2 and 3 respectively illustrate a front view, a side view and a top view of the reactor; • Figure 4 illustrates a top view of the centrifuge; • Figures 5 and 6 respectively illustrate a side view and a front view of the carrier device with centripetal valve;
• Figures 7, 8 and 9 respectively illustrate a side view, a front view and a top view of the carrier device with centrifugal drainage
• Figures 10 and 11 respectively illustrate a side view and a front view of the capillary support device.
• the invention relates to a reactor (1), illustrated in FIGS. 1 to 3, for biological analysis by biochips (2) characterized in that the biochip (2) is movable relative to a surface which faces it between a first position in which the biochip (2) is close to a surface to define a first volume of small container, and a second position in which the biochip is moved away from said surface to define a dynamically variable volume.
• the reactors (1) are aligned and inclined so that the biochips (2) can directly receive the dispensed reagents.
• the body (3) of the reactor has a guide on one of its two large faces. It can also on one of the perpendicular faces include an orifice closed by a plug from the inside, held in abutment by a spring. This orifice is connected to a pipe which allows a liquid under pressure to be injected into the reactor
• a sliding piece (4) supporting biochips which when it is provided with the biochip and fully engaged in its guide, closes one of the two large faces of the reactor.
• the biochip support can be moved one or two millimeters in its guide, without affecting the tightness of the reactor, to improve the contact of deposits with reagents. It can be moved away from its original position to the outside by six or seven millimeters to open the reactor and allow the flow of its contents. Finally, it can be moved away from its original position by a few centimeters to leave the enclosure and place itself in the field of the signal acquisition system. It is the mechanical translation device mentioned above which actuates the biochip supports or in other cases the reactors.
• An agitator (5) composed of a strip (6) which can either rest on the lower part of the biochip (2) forming a solid angle which retains a small volume of liquid, or from this position come to apply on the biochip "spreading" on its surface and without air bubble the volume of liquid retained, or enter completely into the body of the reactor to allow the sliding of the biochip support.
• the continuous passage between these three positions causes the washing liquid to be projected onto the active surface of the biochip.
• reactors can be designed, such as for example the three versions of carrier devices (10) presented in FIGS. 5 and 6, 7 to 9 and 10 and 11. They are simpler and less expensive to produce, but do not not allow you to approach the active surface of the biochip very closely for signal acquisition. In this case, the entire reactor is pushed outside the enclosure of the centrifuge.
• the biochip consists of a glass slide, like microscope slide, on which a hydrophobic paint frame of two to three millimeters in width and regular thickness has been deposited. One side of this frame is interrupted to allow the passage of liquids down the biochip.

Landscapes

• Life Sciences & Earth Sciences (AREA)
• Health & Medical Sciences (AREA)
• General Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Analytical Chemistry (AREA)
• Biochemistry (AREA)
• Physics & Mathematics (AREA)
• General Physics & Mathematics (AREA)
• Immunology (AREA)
• Pathology (AREA)
• Engineering & Computer Science (AREA)
• Biomedical Technology (AREA)
• Molecular Biology (AREA)
• Apparatus Associated With Microorganisms And Enzymes (AREA)
• Automatic Analysis And Handling Materials Therefor (AREA)

Applications Claiming Priority (3)

Publications (1)

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Family Applications (1)

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Family Cites Families (9)

• 2000
  • 2000-03-09 FR FR0003139A patent/FR2806166B1/fr not_active Expired - Fee Related
• 2001
  • 2001-03-09 AU AU39373/01A patent/AU3937301A/en not_active Abandoned
  • 2001-03-09 EP EP01913977A patent/EP1261850A1/de not_active Withdrawn
  • 2001-03-09 WO PCT/FR2001/000717 patent/WO2001067065A1/fr not_active Application Discontinuation
• 2002
  • 2002-09-09 US US10/238,863 patent/US20030059930A1/en not_active Abandoned

Non-Patent Citations (1)

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