Chemical apparatus and process disinfecting – deodorizing – preser – Control element responsive to a sensed operating condition
Reexamination Certificate
2000-02-09
2002-08-06
Drodge, Joseph W. (Department: 1723)
Chemical apparatus and process disinfecting, deodorizing, preser
Control element responsive to a sensed operating condition
C015S302000, C015S303000, C015S320000, C134S044000, C134S085000, C134S088000, C204S600000, C422S063000, C435S287300
Reexamination Certificate
active
06428752
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 “Lab on a Chip” or 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, while it is important to avoid contamination in progressing from work with one material to another.
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 can be hard to clean. 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, and to maintain such instrument clean and avoid contamination of the procedure.
SUMMARY OF THE INVENTION
One purpose of the invention is to provide a technology adapted to the deposition of very small drops of fluids, 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, and at correspondingly high densities. (As used in this application, the term fluid “drop” refers to a very small quantity of fluid, and not to any particular shape of the fluid volume). The fluids and the resultant dots permissibly exhibit a wide range of properties such as viscosity, evaporative characteristics, surface tension, wettability, surfactant characteristic, dynamic contact angle and free surface energy. These and numerous other objectives are achieved by a number of broad features and preferred embodiments which are individually novel and important and which in many cases cooperate in novel ways to achieve highly effective results.
According to one aspect of the invention, an apparatus for depositing fluid dots on a receiving surface in an array suitable e.g., for microscopic analysis reaction and the like, is provided, comprising a deposit device and a fluid source which are cooperatively related to enable the deposit device to precisely size a drop of fluid of small diameter on a drop-carrying surface of the device, transport mechanism for positioning the device at a precisely referenced lateral position over the receiving surface and drive mechanism for moving the deposit device, relatively, in deposition motion toward and away from the surface, the apparatus adapted, by repeated action, to deposit the drops of fluid precisely in a desired array, and then to proceed to a cleaning station where the instrument is cleaned and then to a resupply station for further action with regard to other materials, free of contamination, preferably the apparatus being computer controlled.
Preferred embodiments have one or more of the following features.
A cleaning station comprises a fluid jet arranged to blow down along the length of the deposit device toward its drop-depositing end, the jet and device being within a confinement chamber.
The deposit device is a pin or pin-like structure having an end surface that carries the fluid drop, preferably the pin or pin-like structure having sides that intersect with the end surface to define a sharp peripheral drop-defining rim.
Another broad aspect of the invention is an apparatus for depositing fluid drops on a receiving surface per se, comprising a deposit device and a fluid source which are cooperatively related to provide to a drop-carrying surface of the deposit device a precisely sized drop of fluid, and a cleaning system that effectively cleans the pin, the deposit device being a pin or pin-like structure having an end surface that serves as the drop-carrying surface, the pin or pin-like structure having sides that intersect with the end surface to define a sharp peripheral drop-defining rim.
Preferred pins or pin-like structures have an end surface that is generally flat and side surfaces that are cylindrical and smooth.
In many important cases, the fluid source is a mobile fluid storage device that is movable relative to an array of deposit locations, the fluid storage device being constructed and arranged to resupply the deposit device at various locations along the array.
Another broad aspect of the invention is an apparatus for depositing fluid drops on a receiving surface, comprising a deposit device and a fluid source which are cooperatively related to provide to the deposit device a drop of fluid, transport mechanism for positioning the deposit device over a receiving surface and drive mechanism for moving the deposit device, relatively, in deposition motion toward and away from the receiving surface, the apparatus adapted, by repeated action, to deposit the drops of fluid in a desired array, the fluid source being a mobile fluid storage device that is movable relative to the array of deposit locations, the fluid storage device being constructed and arranged to resupply the deposit device at various locations along the array, the system adapted to effectively clean the instruments between changes of fluids.
In preferred embodiments employing a mobile storage device, the deposit device and the mobile storage device are constructed to supply drops to the deposit device in the immediate vicinity of the deposit locations for respective drops, preferably the mobile fluid storage device and the deposit device being coupled for transverse motion relative to the array and decoupled for movement of the deposit device toward and away from the receiving surface.
In many cases the mobile storage devices are preferably constructed and arranged to be replenished from a remotely located large reservoir.
In many cases a mobile storage device holds a volume of fluid having a free surface into which the deposit device is lowered and raised to obtain a fluid drop, preferably the mobile storage device being constructed to store a multiplicity of isolated fluid volumes in the wells of a multiwell plate, the apparatus constructed to obtain its fluid from a selected volume of the plate.
In other important cases a mobile storage device defines a generally annular fluid retention surface or ring (the term “annular” or “ring” being used to refer broadly to a member that has opposed, or adjacent, surfaces that can hold a mass of fluid between them by surface tension effects, accessible to a deposit device), and the deposit device is const
Affymetrix Inc.
Drodge Joseph W.
McGarrigle Philip L.
Sherr Alan B.
Zitkovsky Ivan D.
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