Chemistry: analytical and immunological testing – Including sample preparation – Volumetric liquid transfer
Reexamination Certificate
1998-09-09
2001-10-30
Ludlow, Jan (Department: 1743)
Chemistry: analytical and immunological testing
Including sample preparation
Volumetric liquid transfer
C073S864010, C101S494000, C141S031000, C422S105000, C436S049000, C436S054000, C436S176000
Reexamination Certificate
active
06309891
ABSTRACT:
INTRODUCTION
1. Field of the Invention
The invention is in the field of capillary printing systems and their fabrication.
2. Background
The accurate dispensing and deposition on a substrate of small volumes of liquid has been effected with a variety of printing instruments including micropipettes and injectors (see, e.g. U.S. Pat. Nos. 4,815,325; 5,601,980; 5,747,102), ink-jet printers (see, e.g. U.S. Pat No. 5,338,688), and fountain-pen type contact-deposition capillaries (see, e.g. WO95/35505 and U.S. Pat. No. 5,770,151). In addition, a number of multiport liquid transfer and delivery apparatuses are commercially available (e.g. MICROLAB® DNA Workstation by Hamilton Co., Reno Nev.; HYDRA Microdispenser by Robbins Scientific, Sunnyvale Calif.; Microarray Printing System by Genometrix, The Woodlands, Tex.). While some of these instruments have been used to print ordered analytical or probe arrays, they offer various relative advantages and disadvantages, including differing print resolution, speed, cross-contamination control, probe tolerances, etc. For example, the cartridges utilized in ink-jet printers dispense a controlled volume of liquid by use of a pressure wave created within the cartridge and which results from a sharp temperature increase to the ink that can damage or sheer a molecularly fragile probe. Existing pipettors and contact deposition capillaries are better suited to printing fragile probes but require washings between different probe loadings and offer limited print resolution. The present invention provides improved printing systems particularly suited for printing high-density analytical arrays.
SUMMARY OF THE INVENTION
The invention provides printing systems and methods for depositing small volumes of liquid on solid substrates. These systems and methods are useful with a wide variety of liquids and substrates and offer a wide variety of applications, including the deposition of arrays of analytes, such as chemical and biochemical library arrays.
In one embodiment, the invention provides a printing system comprising a pod, a detachable printing device, a substrate, a positioner and a preservation device, wherein (a) the pod comprises a receptacle for reversibly attaching an attachment portion of the printing device; (b) the printing device comprises a reservoir containing a liquid comprising a predetermined agent and in fluid connection with the reservoir, a capillary comprising an axial bore having proximal and distal openings to ambient pressure and a printing tip comprising the distal opening and which prints the agent on the substrate; (c) the positioner moves the pod relative to the substrate; and (d) the preservation device is within, containing or in contact with the printing device and preserves the capability of the printing device to print the agent on the substrate over long-term storage. Generally, the preservation device provides a deterrent to evaporation of the liquid, such as a hermetic barrier, a refrigerator, a humidifier, a hygroscopic agent, etc. The system may also comprise a detachable ganged plurality of such printing devices.
In another embodiment, the invention provides a printing system comprising a pod, a detachable ganged plurality of printing devices, a substrate and a positioner, wherein (a) the pod comprises a receptacle for reversibly attaching an attachment portion of the printing devices; (b) each of the printing devices comprises a reservoir containing a unique agent and in fluid connection with the reservoir, a capillary comprising an axial bore having proximal and distal openings to ambient pressure and a printing tip comprising the distal opening and which prints the agent on the substrate; and (c) the positioner moves the pod relative to the substrate.
In another embodiment, the invention provides a printing system comprising a wire bonding capillary containing a predetermined agent and comprising an axial bore having proximal and distal openings to ambient pressure and a printing tip comprising the distal opening and which prints the agent. And in a more particular embodiment, the invention provides a printing system comprising a ganged plurality of wire bonding capillaries, each containing a different agent and comprising an axial bore having proximal and distal openings to ambient pressure and a printing tip comprising the distal opening and which prints the agent.
A wide variety of more particular embodiments of these systems are disclosed. For example, in one such embodiment, the capillary bore tapers toward the distal opening of the tip; in another, the system further comprises a motion resistor operatively joined to the capillary and providing an incomplete resistance to motion of the capillary along its longitudinal axis, wherein the resistance may be provided by springs, an elastomeric membrane, the weight of the capillary, etc.; in another, the printing device is of one-piece construction; in another, the system further comprises a register comprising a guide which contacts a registration portion of the printing device, distal to the attachment portion, and moves the tip relative to the substrate; etc.
The invention provides methods of making, using and storing the subject systems including methods for printing liquids comprising agents or analytes on substrates with the printing systems, particularly printing methods which comprise the step of decelerating the capillary to move the liquid through the bore, out the tip and onto the substrate, which method may be effected, for example, by tapping the tip onto the substrate.
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Bevirt Joeben
Maurino Joseph R.
Shalon Tidhar D.
Titsworth Loren D.
Incyte Genomics Inc.
Ludlow Jan
Osman Richard Aron
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