Chemistry: analytical and immunological testing – Including sample preparation
Reexamination Certificate
2002-07-20
2003-10-28
Drodge, Joseph (Department: 1723)
Chemistry: analytical and immunological testing
Including sample preparation
C118S300000, C134S022100, C134S044000, C134S050000, C134S085000, C422S063000, C422S105000, C436S180000
Reexamination Certificate
active
06638770
ABSTRACT:
BACKGROUND OF THE INVENTION
The invention relates to devices and systems that deposit small quantities of fluid upon substrates in a precise manner and in arrays of desired density and consistency, and especially to cleaning such systems and other equipment in the laboratory. The invention is useful, for instance, in preventing cross-contamination when carrying out reactions, in providing accurate overlays of deposits, and, in particular, in preparing microscope slides and membranes with biological materials, for instance, microarrays for drug delivery, gene research and clinical use.
In well developed biological analytical technology, and in recently developed biochip technology, creation of dense arrays of fluorescently labeled micro-organisms and DNA assays in a two dimensional field is performed. It is desirable to place the arrays on a conventional microscope slide, or other carrier and to create many such slides simultaneously in a manufacturing process.
For biochip technology to proceed to complete fruition, as well as to improve the application of previous analytical techniques, economical instruments and systems have been needed that can, without contamination, rapidly and accurately create the dense array of objects over a large field portion of a glass microscope slide or a slide-like member that occupies an area approximately 22 mm wide and 50 mm long of a slide that is nominally 25 mm×75 mm.
In the deposition upon a microscope slide of discrete, minute quantities of a large variety of fluid materials, the volume deposited at a discrete spot typically may be from a few pico liter to a fraction of a micro liter, depending upon the application. The devices for forming such deposits are small and may have high surface energy. The biological material carried in this fluid can range from a few strands of short oligonucleotides in a water solution to a high concentration of long strands of complex proteins. The properties of these fluids vary enormously. Some are akin to water while others are far more viscous, resembling a light oil or honey. The range of fluids that may be employed also exhibits wide differences in other properties that make clean up difficult.
Such a large range of property variations in fluids of interest has caused difficulties for any single type of process to operate over a wide range to produce the desired array of deposits, to maintain such instrument clean and avoid contamination of the deposited array, the used biological material and various fluids used for deposition.
SUMMARY OF THE INVENTION
One purpose of the invention is to provide a technology deposition of very small drops of fluids, and arrays of drops, e.g. drops that form spots of less than about 375 or 300 &mgr;m diameter, and in important cases, very much smaller than that, deposited at correspondingly high densities. As used in this application, the term fluid “drop” refers to a very small quantity of fluid or fluid including solid material, and not to any particular shape of the fluid volume. When depositing an array of drops, it is important to avoid contamination in progressing from work with one material to another as well as contamination of the source material.
The present invention relates to methods and apparatuses used for depositing a biological or other material on a receiving surface and creation of an array. The deposited array is suitable for sample acquisition, preparation microscopic analysis, reaction or other purposes. The deposited array is useful in a variety of biological applications some of which are described in U.S. Pat. Nos. 4,965,188; 5,143,854; 5,384,261; 5,856,174, which are incorporated by reference.
According one aspect, an apparatus for depositing an array of spots on a receiving surface includes a fluid source (or source means), a deposit device that includes a drop-carying surface (or deposit means), and a cleaning device (or cleaning means). The deposit device and a fluid source are cooperatively arranged to deposit a spot (usually created by a drop) on a receiving surface. The cleaning device is constructed and arranged to clean the drop-carying surface by employing a flow of cleaning fluid (or another cleaning matter such as small particles). , The apparatus may include additional optional elements discussed below and/or shown in the drawings. The cleaning device may include a fluid jet constructed and arranged to blow the cleaning fluid. The fluid jet may be constructed and arranged to blow,the cleaning fluid at least partially along a length of the deposit device toward the drop-carrying surface. The drop-carrying surface may be located at least partially within a confinement chamber.
The deposit device may have a pin-like structure with the drop-carrying surface disposed in a distal end of the pin-like structure. The drop-carrying surface may have a diameter less than 375 micron, preferably less than 300 micron, preferably between about 15 and 250 micron. The pin-like structure may include sides that intersect with an end surface that defines a rim of the drop-carrying surface.
The apparatus may include one or several fluid sources. The fluid source may include or be used with a mobile supply device, associated with the deposit device, and arranged to supply material for deposition of the array of spots. The fluid source may include or be used with a mobile local supply device arranged to move partially with the pin-like structure. The deposit device and the mobile supply device may be movable together to the cleaning device in response to a control system.
The mobile local supply device may include an annular member through which the deposit device operates by a relative motion of the drop-carrying surface, and the cleaning device may include a nozzle for directing a flow of the cleaning fluid past the annular member and the drop-carrying surface.
The apparatus may include one or several cleaning devices. The cleaning device is constructed and arranged to deliver the cleaning fluid at least partially to the mobile supply device or the mobile local supply device. The mobile local supply device includes a ring-like structure located near the drop-carrying surface. The cleaning device may be constructed and arranged to deliver the cleaning fluid at least partially to the ring-like structure and the drop-carrying surface.
The apparatus may further include a drying device constructed to discharge drying fluid. Alternatively, the drying device is included in the cleaning device and is constructed to discharge drying fluid using the fluid jet used for cleaning. The fluid jet may have various designs and may include a circular nozzle constructed to emit a conical flow of the cleaning or drying fluid achieving venturi effect, or may include an annular or other nozzle.
The apparatus may further include a reservoir for receiving the cleaning or drying fluid. A vacuum pump or another pumping device may be associated with the reservoir. The reservoir receives the cleaning or drying fluid emitted from the fluid jet. The fluid jet or nozzle may be located inside a containment chamber or outside the chamber. The pump may create a pressure differential for removing the cleaning or drying fluid emitted from the fluid jet.
The apparatus may include two or more fluid paths associated with at least two fluid reservoirs and connectable to the fluid jet. The apparatus may be associated with a control system arranged to control a flow velocity of the cleaning fluid. The apparatus may be associated with a control system arranged to select a type of the cleaning fluid. The control system may be arranged to select the type of the cleaning fluid at a source location. The cleaning fluid is selected from one of the following compressed gas, high-pressure liquid, aerosol and heated gas.
The apparatus may include four or more deposit devices and a mechanism for moving each deposit device independently toward and away from the receiving surface to deposit respective drops at respective deposit locations on the receiving surface. Alternatively, the mechanism may move
Affymetrix Inc.
Drodge Joseph
McGarrigle Philip L.
Zitkovsky Ivan D.
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