Classifications

• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
  • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
  • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
  • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
  • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
  • G01N33/54366—Apparatus specially adapted for solid-phase testing
• • 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
  • B01J2219/00653—Making arrays on substantially continuous surfaces the compounds being bound to electrodes embedded in or on the 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
  • B01J2219/0068—Means for controlling the apparatus of the process
  • B01J2219/00702—Processes involving means for analysing and characterising the products
• • 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
  • B01J2219/00718—Type of compounds synthesised
  • B01J2219/0072—Organic compounds
  • B01J2219/00722—Nucleotides
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
  • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
  • B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
• • C—CHEMISTRY; METALLURGY
  • C40—COMBINATORIAL TECHNOLOGY
  • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
  • C40B40/00—Libraries per se, e.g. arrays, mixtures
  • C40B40/04—Libraries containing only organic compounds
  • C40B40/06—Libraries containing nucleotides or polynucleotides, or derivatives thereof
• • 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

• the invention relates to a housing for an electronic chip with biological probes, in particular for molecular analysis of DNA, said housing comprising a flat support device provided with an access window to a matrix of 'electrodes constituting the active part of the chip.
• a DNA chip is formed by a silicon substrate on which is deposited one or a plurality of sequence (s) of biological probes, formed by an array of electrodes and counter-electrodes, each having reduced dimensions, of the order of 50X50 microns.
• sequence s
• the distribution of the probes at particular points on the substrate takes place according to known methods described in documents US-A-5 143 854 and WO 92/10092.
• Each probe is addressable on the other hand by an electronic circuit with demultiplexing integrated on the substrate, so that all the points of the matrix constitute the image of a multitude of known DNA sequences relating to specific types of virus.
• the solution containing the DNA of the patient is deposited on the chip, and it then forms at certain points on the substrate, chemical bonds which are revealed by a fluorescence effect.
• the object of the invention is to provide an electrical connection between the biological chip and a connection device accessible on the housing, and to obtain optimum protection of the chip with respect to a given environment.
• the support device is formed by assembling a first lower support and a second upper support, one of which is equipped with a connector for activating the chip,
• a plurality of electrical connections extends along the interface for assembling the first and second supports between the connector and the chip
• electrical connection means are arranged to ensure the continuity of the electrical connections with conductive tracks of the chip
• - And protection means are placed in the environment of the chip to obtain an effect of electrical and biological isolation of the active part with respect to the input and output contacts of the connector.
• the connector contacts and electrical connections are made on one of the supports by means of a printed circuit or conductive screen printing. It is also possible to use a soft ribbon attached to one of the supports.
• the means of electrical connection between the electrical connections and the chip are produced either by welding a conductive wire, or by fusion on the chip of a fusible tin-lead chip, or by interposition of double-sided adhesive strips of conductive elastomeric material.
• the box is characterized in that: the connector and the electrical connections are located with the chip on the first lower support of the box,
• the chip projects into the window provided in the second upper support, and has larger dimensions than the chip
• a protective layer based on resin is put in place in said window to completely coat the electrical connection means, and the empty part of the cutout framing the periphery of the chip.
• the box is characterized in that: the connector and the electrical connections are arranged on the second upper support, which is provided with the window having a dimension smaller than the chip,
• the first lower support is equipped with a groove for housing the chip, the thickness of said chip being less than the depth of said groove,
• a bridging interval is provided between the chip and the first support for receiving a seal, and electrical connection means.
• a viewing prism is advantageously incorporated in the window for deflecting an incident reading laser beam in a parallel direction above the probes of the chip.
• the housing contains a plurality of chips accessible from a single window and connected to the same connector. The chips can be integrated into a semiconductor substrate.
• FIG. 1 is a sectional view of a housing housing an electronic chip according to the invention
• FIG. 1 is a plan view of the housing of Figure 1;
• FIG. 5 is a plan view of a multiple chip package
• FIG. 6 shows a sectional view of a housing containing a substrate
• Figure 7 is a plan view of Figure 6.
• a housing 10 for housing a biological DNA chip 12 comprises a first lower support 14 on which the chip 12 is stuck, and a second upper support 16 provided with an access window 18 to the active face 20 of the chip 12.
• the window 18 is formed by a rectangular cutout 22 crossing the entire thickness of the second support 16, and having a larger surface than that of the chip 12.
• the active face 20 of the chip 12 comprises a matrix of metal electrodes, in particular of gold, distributed at particular points of the silicon substrate to constitute the different biological probes.
• the abutment face 24 of the first support 14 with the adjacent internal face 26 of the second upper support 16 is provided with a plurality of electrical connections 28 extending along the interface for assembling the supports 14, 16 in being connected to contacts 30 of a connector 32 arranged at the end of the first lower support 14.
• the electrical connections 28 and the contacts 30 of the connector 32 on the first support 14 can be produced by various known methods, using in particular the technology of printed circuits, screen printing, or an attached flexible ribbon cable.
• the second upper support 16 with window 18 covers the abutment face 24 of the first support 14, except at the location of the connector 32 which remains accessible with the active surface 20 receiving the reactive liquid and the DNA to be checked.
• the ends of the electrical connections 28 are positioned inside and at the bottom of the window 18, and are connected to conductive tracks formed on the active face 20 of the chip 12 by means of electrical connection 34.
• these electrical connection means 34 are produced by ultrasonic welding of a conductive wire of aluminum or gold. This “bonding” operation can of course be replaced by other methods depending on the technology of the chip 12.
• the seal is obtained by means of a protective layer 36 of thermosetting resin placed in the window 18 until covering the edges of the chip 12, so as to completely coat the electrical connection means 34, and the part void of the cutout 22 framing the periphery of the chip 12.
• the material of the protective layer 36 is an electrical insulator, and has neutral biological properties or compatible with pyrrole. This results in an electrical and biological isolation effect of the active part 20 of the chip 12 with respect to the contacts 30 of inputs and outputs of the connector 32.
• the housing 100 includes a first lower support 114 equipped with a groove 102 in which is housed the biological DNA chip 112, the thickness of the chip 11 2 being less than the depth of the groove 102.
• a second upper support 116 covers the entire surface of the first lower support 1 14, and is provided with a window 118 arranged opposite the active part 120 of the chip 112. The dimension of the window 118 is in this case less to that of chip 112.
• the electrical connections 128 connected to the contacts 130 of the connector 132 are arranged on the second upper support 116, and extend to the interior of the groove 102, being separated from the chip 112 by a bridging interval 106 having a small thickness.
• the electrical connection means 134 between the electrical connections 128 and the chip 112 are obtained for example by the "flip chip” process consisting in melting on the chip a fusible tin-lead chip subject to electrical contact. It is also possible to make use of double-sided adhesive strips of conductive elastomeric material, the thickness of the strips corresponding to the bridging interval. In the case of chips with metallized holes, the electrical contact can be made on the face opposite to the active part 120.
• the active part 120 is sealed by means of a seal 104 having a dimension slightly greater than that of the window 118, and interposed between the chip 112, and the second support 116 above the right of the window 118.
• the gasket material 104 is chosen to be biologically compatible with the pyrrole. It is also possible to ensure sealing by injecting a polymerizable resin, and biologically compatible in the interval 106 ..
• the protective layer 136 is housed in the groove 102 surrounding the side edges and the underside of the chip 1 12 opposite the active part 120.
• the glass plate 138 covers the window 118 as in the case of the figure 1. After the encapsulation of the chip 12, 112 in the respective housing 10, 100, the active part 20, 120 remains accessible for depositing the pyrrole-based liquid with the DNA to be tested, while guaranteeing its electrical and biological isolation relative to the contacts 30, 130 of the respective connector 32, 132.
• the housing 10 additionally contains a viewing prism 150 intended to deflect a reading laser beam FL directed perpendicularly to the glass plate 38.
• the prism 150 is arranged in the window 18 between the protective layer 36 and the internal face of the glass plate 38.
• the hypotenuse of the prism 150 returns the incident laser beam FL in a parallel direction above the probes of the chip 12.
• the incorporation of the prism 150 under the glass plate 38 makes it possible to '' improve the reading of the biological analysis during reception and emission of the laser beam.
• a window 218 gives access to several biological DNA chips 212 incorporated in the same housing 200 to increase the number of probes. Electrical connections (not shown) connect the different chips 212 to the same connector 232.
• a housing 300 of cylindrical shape serves as a housing for the semiconductor substrate 312 accessible from a cylindrical window 318, and connected to the connector 332 by electrical connections 334.

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• Health & Medical Sciences (AREA)
• Immunology (AREA)
• Life Sciences & Earth Sciences (AREA)
• Engineering & Computer Science (AREA)
• Molecular Biology (AREA)
• Biomedical Technology (AREA)
• Chemical & Material Sciences (AREA)
• Hematology (AREA)
• Urology & Nephrology (AREA)
• Biotechnology (AREA)
• Microbiology (AREA)
• Cell Biology (AREA)
• Food Science & Technology (AREA)
• Medicinal Chemistry (AREA)
• Physics & Mathematics (AREA)
• Analytical Chemistry (AREA)
• Biochemistry (AREA)
• General Health & Medical Sciences (AREA)
• General Physics & Mathematics (AREA)
• Pathology (AREA)
• Apparatus Associated With Microorganisms And Enzymes (AREA)

Applications Claiming Priority (3)

Publications (2)

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• 1998
  • 1998-10-20 FR FR9813339A patent/FR2784751B1/fr not_active Expired - Fee Related
• 1999
  • 1999-10-20 US US09/807,901 patent/US6663837B1/en not_active Expired - Fee Related
  • 1999-10-20 EP EP99949083A patent/EP1144680A3/de not_active Withdrawn
  • 1999-10-20 WO PCT/FR1999/002553 patent/WO2000023617A2/fr not_active Application Discontinuation

Non-Patent Citations (1)

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