Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid
Reexamination Certificate
1999-07-22
2001-01-30
Brusca, John S. (Department: 1631)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving nucleic acid
C707S793000
Reexamination Certificate
active
06180351
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to arrays, particularly biopolymer arrays (such polynucleotide arrays, and particularly DNA arrays) which are useful in diagnostic, screening, gene expression analysis, and other applications.
BACKGROUND OF THE INVENTION
Arrays of biopolymers, such as arrays of peptides or polynucleotides (such as DNA or RNA), are known and are used, for example, as diagnostic or screening tools. Such arrays include regions (sometimes referenced as features or spots) of usually different sequence biopolymers arranged in a predetermined configuration on a substrate. The arrays, when exposed to a sample, will exhibit a pattern of binding which is indicative of the presence and/or concentration of one or more components of the sample, such as an antigen in the case of a peptide array or a polynucleotide of particular sequence in the case of a polynucleotide array. The binding pattern can be detected by interrogating the array, for example, by observing a fluorescence pattern on the array following exposure to a fluid sample in which all potential targets (for example, DNA) in the sample have been labeled with a suitable fluorescent label.
Biopolymer arrays can be fabricated using either in situ synthesis methods or deposition of the previously obtained biopolymers. The in situ synthesis methods include those described in U.S. Pat. No. 5,449,754 for synthesizing peptide arrays, as well as WO 98/41531 and the references cited therein for synthesizing polynucleotides (specifically, DNA). Such in situ synthesis methods can be basically regarded as iterating the sequence of depositing droplets of: (a) a protected monomer onto predetermined locations on a substrate to link with either a suitably activated substrate surface (or with a previously deposited deprotected monomer); (b) deprotecting the deposited monomer so that it can now react with a subsequently deposited protected monomer; and (c) depositing another protected monomer for linking. Different monomers may be deposited at different regions on the substrate during any one iteration so that the different regions of the completed array will have different desired biopolymer sequences. One or more intermediate further steps may be required in each iteration, such as oxidation and washing steps.
The deposition methods basically involve depositing biopolymers at predetermined locations on a substrate which are suitably activated such that the biopolymers can link thereto. Biopolymers of different sequence may be deposited at different regions of the substrate to yield the completed array. Washing or other additional steps may also be used. Typical procedures known in the art for deposition of polynucleotides, particularly DNA such as whole oligomers or cDNA, are to load a small volume of DNA in solution in one or more drop dispensers such as the tip of a pin or in an open capillary and, touch the pin or capillary to the surface of the substrate. Such a procedure is described in U.S. Pat. No. 5,807,522. When the fluid touches the surface, some of the fluid is transferred. The pin or capillary must be washed prior to picking up the next type of DNA for spotting onto the array. This process is repeated for many different sequences and, eventually, the desired array is formed. Alternatively, the DNA can be loaded into a drop dispenser in the form of an inkjet head and fired onto the substrate. Such a technique has been described, for example, in PCT publications WO 95/25116 and WO 98/41531, and elsewhere. This method has the advantage of non-contact deposition. Still other methods include pipetting and positive displacement pumps such as the Biodot equipment (available from Bio-Dot Inc., Irvine Calif., USA).
In array fabrication, the quantities of DNA available for the array are usually very small and expensive. Sample quantities available for testing are usually also very small and it is therefore desirable to simultaneously test the same sample against a large number of different probes on an array. These conditions require use of arrays with large numbers of very small, closely spaced spots. Due to the precision required, and to maintain costs low, while end users may design their own array layout it will often be desirable to have the arrays fabricated at a fabrication facility and then shipped to the end user. Since the end user designed the array, they will have array layout information available to them at their own location. However, when an array corresponding to the array layout is received from the fabrication facility, some type of identification should be provided on the array substrate or a housing containing the array which allows matching that array to the layout information, since array layout information in some form is used to meaningfully interpret the information obtained from interrogating the array. Unique identifiers and their generation have been previously described, such as in U.S. Pat. No. 5,812,793, U.S. Pat. No. 5,404,523, and the references cited therein. Such unique identifiers (often referred to as “Globally Unique Identifiers” or “GUIDs”, or “Universally Unique Identifiers” or “UUIDs”) can, for example, include a network card identification which is specific to that card, along with a time and local counter number, and other components. Use of such unique identifiers in association with array layouts generated at the same or different locations, would virtually eliminate the possibility of the same identifier being associated with different array layouts. However, such unique identifiers typically require 128 bit data string. A string of such length when written, for example, as a bar code, typically takes up about 3 to 4 cm, which is more room than is often available on a substrate adjacent a typical array (which may be less than about 1 cm in any dimension).
It would be desirable then, if there was a way in which unique identifiers, such as GUIDs or UUIDs could still be associated with array layouts but without requiring, on an array or its housing, an amount of space (whether physical or data string length) normally occupied when such unique identifiers are written.
SUMMARY OF THE INVENTION
The present invention then, realizes that unique identifiers can still be associated with an array, without requiring the same amount of space on the array or its housing, which are normally required by such unique identifiers. In particular, the present invention realizes that this can be accomplished by using a second identifier of shorter length than a corresponding unique identifier, and which is associated in some manner with the unique identifier.
In one aspect then, the present invention provides a method of generating an addressable array of chemical moieties on a substrate. The chemical moieties may particularly include biopolymers, for example polynucleotides (such as DNA or RNA) or peptides. The method includes obtaining information on a layout of the array (such as from a remote site or locally, for example from a local memory). An identifier corresponding to the array layout information is also obtained. The addressable array is fabricated on the substrate in accordance with the layout information. The identifier is applied to the substrate carrying the array (such as, for example, writing the identifier directly onto the substrate).
In another aspect, the present invention provides a method of generating an addressable array of chemical moieties on a substrate. The method includes receiving from a remote station, information on a layout of the array and an associated unique identifier. A local identifier is generated which corresponds to the unique identifier and associated array, the local identifier being shorter in length than the corresponding unique identifier. The addressable array is fabricated on the substrate in accordance with the received layout information. A first copy of the local identifier is applied to the substrate or a housing carrying the substrate. The fabricated array and the first copy of the local identifier are then shipped to a remote station.
Agilent Technologie,s Inc.
Brusca John S.
Kim Young J.
Stewart Gordon
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