Chemistry: analytical and immunological testing – Including sample preparation – Volumetric liquid transfer
Reexamination Certificate
1998-10-30
2001-05-08
Warden, Jill (Department: 1743)
Chemistry: analytical and immunological testing
Including sample preparation
Volumetric liquid transfer
C436S043000, C436S047000, C436S050000, C436S054000, C422S063000, C422S065000, C422S067000, C422S105000, C422S105000, C073S864220, C073S864230, C073S864240, C073S864250
Reexamination Certificate
active
06228659
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to microarrays of biopolymers or the like formed on a substrate surface, and to an apparatus and method for producing such microarrays.
BACKGROUND OF THE INVENTION
A variety of methods are currently available for making arrays of biological macromolecules, such as arrays of nucleic acid molecules or proteins. One method for making ordered arrays of DNA on a porous membrane is a “dot blot” approach. In this method, a vacuum manifold transfers a plurality, e.g., 96, aqueous samples of DNA from 3 millimeter diameter wells to a porous membrane. This method is not suitable for making microarrays, i.e., arrays in which the different sample regions in the array are separated by distances of about 1 mm or less.
Microarrays may be made by a robotic arm device that moves successively between a sample-pickup well in a sample array, e.g., a microtitre plate, and a selected microarray position. Although high-density arrays of different biological materials can be constructed by this approach, the production time and efficiency is limited by the fact that the regions of the microarray (or microarrays, if several are being constructed at once) are deposited one-by-one in serial fashion.
Methods for making oligomer arrays on a microchip by parallel step-wise subunit addition have been proposed, e.g., Fodor, et al.,
Science
251:767-773 (1991). This approach uses photomasking to selectively deprotect terminal subunit addition sites in selected regions of the array thus allowing massive parallel subunit addition in building the oligomers on the array. This approach, however, requires relatively expensive processing equipment. It is also not readily adapted to constructing arrays of polymers that are more than about 10-15 subunits in length.
It would therefore be desirable to provide an improved method and apparatus for making arrays, particularly microarrays, employing parallel sample deposition.
SUMMARY OF THE INVENTION
The invention includes, in one aspect, apparatus for producing a plurality of arrays of reagent regions, where each array contains a row of n >1 reagent regions. The apparatus includes a work station for supporting a substrate that can be partitioned into a plurality of array areas, a dispensing assembly having a row of N dispensing heads, each disposed to deposit reagent at a selected one of n different reagent regions in different array area.
In operation, the assembly is advanced successively an incremental distance effective to advance an assembly head from one reagent region in one array area to the corresponding reagent region in an adjacent array area, and to position an adjacent assembly head at a corresponding selected reagent region in an adjacent array area, thus to position each assembly head for deposition at its selected position in an adjacent array area. This operation is effective to position each head successively for deposition at a unique region each array area.
In one general embodiment, the assembly is advanced in the direction of the rows in the array areas, and the head-to-head spacing in the assembly is equal to the sum or difference of (i) the spacing between corresponding reagent regions in immediately adjacent array areas and (ii) the spacing between selected reagent regions in a row in an array area. This embodiment may been carried out with an assembly having a two-dimensional array of dispensing heads, allowing two dimensional microarrays to be formed by parallel deposition.
In another general embodiment of the apparatus, the assembly is advanced in the direction normal to rows in the array areas, with the dispensing heads in the assembly being disposed along an axis that is angular offset from the direction of assembly travel.
The dispensing heads may be pins spaced for simultaneous dipping into the wells of a microtitre plate. Here the structure supplying reagents to the pins includes structure for moving the assembly between positions at which the pins in the assembly are dipped in selected wells in the plate, and positions for reagent deposition on the substrate. In another embodiment, the assembly heads are ink-jet printer heads, and the supply structure includes structure for activating the printer heads.
The invention also includes a method for producing a plurality of arrays of reagent regions, where each array contains a row of n >1, i.e., two or more, reagent regions. The method includes placing in a work station, a substrate that can be partitioned into a plurality of array areas, and advancing over the substrate, a dispensing assembly having a row of N dispensing heads, each disposed to deposit reagent at a selected one of the n different reagent regions in different array areas. The advancing is carried out in incremental distances effective to advance an assembly head from one reagent region in one array area to the corresponding reagent region in an adjacent array area, thus to position each assembly head for deposition at a selected region in an array area. At each new position, the assembly heads are activated for deposition on reagent regions in the array areas. The advancing and head activating steps are repeated until all the regions in a selected row in the array areas have reagents deposited thereon.
In one method, the assembly is advanced in the direction of the rows. In this method, the head-to-head spacing in the assembly is equal to the sum or difference of (i) the spacing between corresponding reagent regions in immediately adjacent array areas and (ii) the spacing between selected regions in a row in an array area. This method may be carried out with an assembly having a two-dimensional array of dispensing heads, allowing two dimensional microarrays to be formed by parallel deposition.
In another embodiment of the method, the assembly is advanced in the direction normal to rows in the array areas, with the adjacent heads in the assembly being disposed along an axis that is angularly offset from the from the direction of assembly travel.
These and other objects and features of the invention will become more fully apparent when the following detailed description of the invention is read in conjunction with the accompanying drawings.
REFERENCES:
patent: 3164304 (1965-01-01), Jager et al.
patent: 3329964 (1967-07-01), Mutschler et al.
patent: 3334354 (1967-08-01), Mutschler
patent: 3568735 (1971-03-01), Lancaster
patent: 3843053 (1974-10-01), Thoden
patent: 4023716 (1977-05-01), Shapiro
patent: 4165646 (1979-08-01), Shapiro
patent: 4351799 (1982-09-01), Gross et al.
patent: 4681742 (1987-07-01), Johnson et al.
patent: 4699884 (1987-10-01), Noss et al.
patent: 4731335 (1988-03-01), Brigati
patent: 4952518 (1990-08-01), Johnson et al.
patent: 5000921 (1991-03-01), Hannaway et al.
patent: 5011779 (1991-04-01), Maimon
patent: 5046539 (1991-09-01), MacLeish et al.
patent: 5226462 (1993-07-01), Carl
patent: 5262128 (1993-11-01), Leighton et al.
patent: 5338688 (1994-08-01), Deeg et al.
patent: 5443791 (1995-08-01), Cathcart et al.
patent: 5508200 (1996-04-01), Tiffany et al.
patent: 5525515 (1996-06-01), Blattner
patent: 5540889 (1996-07-01), Gordon et al.
patent: 5551487 (1996-09-01), Gordon et al.
patent: 5601980 (1997-02-01), Gordon et al.
patent: 5677195 (1997-10-01), Winkler et al.
patent: 5736105 (1998-04-01), Astle
patent: 5756050 (1998-05-01), Ershow et al.
patent: 5770151 (1998-06-01), Roach et al.
patent: 5770860 (1998-06-01), Franzen
patent: 5772966 (1998-06-01), Maracas et al.
patent: 5807522 (1998-09-01), Brown et al.
patent: 5849598 (1998-12-01), Wilson et al.
Kowallis Reid B.
Raysberg Yefim M.
Bex Katheryn
PE Corporation (NY)
Warden Jill
Woodcock Washburn Kurtz Mackiewicz & Norris LLP
LandOfFree
Method and apparatus for making arrays does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method and apparatus for making arrays, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method and apparatus for making arrays will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2486819