Chemistry: molecular biology and microbiology – Apparatus – Including measuring or testing
Reexamination Certificate
2002-07-26
2004-06-29
Redding, David A. (Department: 1744)
Chemistry: molecular biology and microbiology
Apparatus
Including measuring or testing
C435S288300, C435S288700, C435S809000, C422S105000, C422S105000, C156S293000
Reexamination Certificate
active
06756224
ABSTRACT:
TECHNICAL FIELD
The present invention relates to a device for receiving a chip shaped carrier having on one side a first surface which includes an active surface coated with an array of DNA snippets or the like, a second surface on a second side opposite to said first side, and an edge having a peripheral outer surface which extends between said first and said second surface, said active surface being adapted to be read by an electro-optical reading device.
The invention further relates to an analytical cartridge comprising a chip receiving device.
The invention further relates to a process for assembling a plurality of such chip receiving devices.
The invention further relates to a system for carrying out evaluation and/or monitoring methods involving electro-optical reading of an active surface of a chip shaped carrier.
The invention further relates to a method for positioning and fastening at least one second object in a first object, the first object being provided with a seat for said at least one second object.
BACKGROUND OF THE INVENTION
Within the context of the instant invention a chip shaped carrier is a substrate, in particular a glass chip of e.g. squared shape having a thickness of e.g. 0.7 or 1.0 millimeter and a so called active surface, which is a surface coated with an array of different snippets of DNA, e.g. DNA oligonucleotide probes, located at known positions on that surface. Those snippets of DNA serve as probes for detecting DNA fragments with a complementary DNA sequence.
Within the context of the instant invention a receiving device for receiving such a DNA chip is in particular a one-way cartridge made of a plastic material, and a cartridge hosting a DNA chip is called an analytical cartridge.
DNA chips contained in such cartridges have a wide range of applications. For example, they may be used for studying the structure-activity relationship between different biological materials or determining the DNA-sequence of an unknown biological material. For instance, the DNA-sequence of such unknown material may be determined by, for example, a process known as sequencing by hybridization. In one method of sequencing by hybridization, sequences of diverse materials are formed at known locations on a surface of a chip, and a solution containing one or more targets to be sequenced is applied to that surface. The targets will bind or hybridize with only complementary sequences on the substrate. The locations at which hybridization occurs are detected with appropriate detection systems by labeling the targets with a fluorescent dye, radioactive isotope, enzyme, or other marker. Information about target sequences can be extracted from the data obtained by such detection systems.
By combining various available technologies, such as photolithography and fabrication techniques, substantial progress has been made in the fabrication and placement of diverse materials on chips of the above mentioned kind. For example, thousands of different sequences may be fabricated on a single substrate of about 1.28 square centimeter in only a small fraction of the time required by conventional methods. Such improvements make these substrates practical for use in various applications, such as biomedical research, clinical diagnostics, and other industrial markets, as well as the emerging field of genomics, which focuses on determining the relationship between genetic sequences and human physiology.
As commercialization of such chips becomes widespread, an economically feasible device and a method for receiving the chips with a high-throughput are desired.
Since the active surface of the chip, that is the surface thereof which is coated with the above mentioned diverse sequences, has to be accessible e.g. to optical detection means, e.g. in the case of fluorescence measurements, the chip has to be inserted into a wall of a one-way cartridge with its active surface facing the interior of the so-called process chamber within the cartridge, and with its opposite surface being accessible to the optical detection means.
For instance in the above mentioned method of sequencing by hybridization, processing of the coating on the active surface of the chip includes flooding of the process chamber of the cartridge with a solution containing one or more targets to be sequenced. Therefore, a liquid-tight connection between the chip and the one-way cartridge is necessary. In a known embodiment described in U.S. Pat. No. 5,945,334 this has been achieved under clean-room conditions by attaching the chip to a cavity of the cartridge by means of an adhesive, that is by gluing it into the cartridge. This known method for connecting the chip to the cartridge has serious disadvantages. First, the fluorescence of the adhesives used is so high that it substantially interferes and perturbates fluorescence measurements performed on the active surface of the chips and can even have saturating effect on a photomultiplier used for performing the fluorescence measurements. The adhesive has to be applied by a dispenser, which is not possible with any adhesive. Furthermore, the known adhesives are prone to develop or contain gases, which when freed would disturb the reactions. Another problem is occasioned by solvent present in the adhesive because the solvent may react with the DNA samples on the active surface. It has even be found that solvent negatively influence the properties of the glass surface of a chip shaped carrier, e.g. blurs it.
A further disadvantage of the known method for connecting the chip to the cartridge is that it is performed manually and is not suitable for being performed by automated means, because a very careful positioning within the receiving window of the cartridge is necessary. Furthermore, as the adhesive is applied thereafter, a second control, if the DNA chip is still in place, has to be performed. These operations are aggravated by the relatively large tolerances of the dimensions of the chips and their rather uneven edges.
BRIEF SUMMARY OF THE INVENTION
A first aim of the invention is therefore to provide a device for receiving a chip of the above mentioned kind which avoids at least one of the above-mentioned disadvantages, and preferably all of it.
A second aim of the invention is to provide an analytical cartridge comprising a chip receiving device according to the invention.
A third aim of the invention is to provide a process for assembling a plurality of chip receiving devices according to the invention with a high throughput.
A fourth aim of the invention is to provide a system for carrying out evaluation and/or monitoring methods involving electro-optical reading of an active surface of a chip shaped carrier with avoiding at least one of the above mentioned disadvantages of prior art embodiments.
A fifth aim of the present invention is to provide a method for more conveniently placing a first object in a second object and to fasten it there.
According to the invention the above-mentioned first aim is attained with a device for receiving a chip shaped carrier having on one side a first surface which includes an active surface coated with an array of DNA snippets or the like, a second surface on a second side opposite to said first side, and an edge having a peripheral outer surface which extends between said first and said second surface, said first surface being adapted to be read by an electro-optical reading device, said device comprising
(a) a cartridge having an opening for introducing a liquid sample into said cartridge,
(b) said cartridge having a casing part which has an outer surface and an inner surface, a first cavity for receiving a chip shaped carrier,
(c) a layer of a sealing material which is reversibly transformable at least once from a solid state into a fluid state and which is provided in a sufficient amount to establish a liquid-tight bond between the inner surface of side walls of the first cavity and said peripheral outer surface of the edge of the chip shaped carrier when the latter is placed into said first cavity.
The main advantages of a chip
Redding David A.
Roche Molecular Systems Inc.
Wise Bart W.
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