U.S. patent application number 09/819172 was filed with the patent office on 2002-05-30 for capillary printing systems.
Invention is credited to Bevirt, JoeBen, Maurino, Joseph R., Shalon, Tidhar D., Titsworth, Loren D..
Application Number | 20020064887 09/819172 |
Document ID | / |
Family ID | 22534841 |
Filed Date | 2002-05-30 |
United States Patent
Application |
20020064887 |
Kind Code |
A1 |
Shalon, Tidhar D. ; et
al. |
May 30, 2002 |
Capillary printing systems
Abstract
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. In particular embodiments, the
systems comprise a preservation device, a detachable ganged
plurality of printing devices, and/or a wire bonding capillary.
Inventors: |
Shalon, Tidhar D.;
(Atherton, CA) ; Maurino, Joseph R.; (Fremont,
CA) ; Titsworth, Loren D.; (Fremont, CA) ;
Bevirt, JoeBen; (Palo Alto, CA) |
Correspondence
Address: |
RICHARD ARON OSMAN
SCIENCE AND TECHNOLOGY LAW GROUP
75 DENISE DRIVE
HILLSBOROUGH
CA
94010
|
Family ID: |
22534841 |
Appl. No.: |
09/819172 |
Filed: |
March 27, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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09819172 |
Mar 27, 2001 |
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09150502 |
Sep 9, 1998 |
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Current U.S.
Class: |
436/180 ; 347/40;
422/400 |
Current CPC
Class: |
B01L 2300/105 20130101;
C40B 40/06 20130101; B01L 2400/021 20130101; G01N 35/1065 20130101;
G01N 2035/00237 20130101; B01L 3/0244 20130101; Y10T 436/119163
20150115; B01J 2219/00596 20130101; B01J 2219/00722 20130101; B01J
2219/00725 20130101; B01L 2200/142 20130101; B01L 2300/10 20130101;
B01J 19/0046 20130101; B01J 2219/00385 20130101; B01J 2219/00369
20130101; B01L 2400/025 20130101; Y10T 436/114998 20150115; B01J
2219/00585 20130101; B01J 2219/00527 20130101; Y10T 436/2525
20150115; B01J 2219/00612 20130101; B01L 3/5085 20130101; C40B
60/14 20130101; B01L 2300/0838 20130101; B01L 2300/1894 20130101;
B01J 2219/00605 20130101; B01J 2219/0061 20130101; B01J 2219/00659
20130101; Y10T 436/2575 20150115; B01J 2219/0036 20130101; C40B
40/10 20130101; B01L 3/0268 20130101 |
Class at
Publication: |
436/180 ;
422/100; 347/40 |
International
Class: |
G01N 001/10; B41J
002/14 |
Claims
What is claimed is:
1. A printing system comprising a detachable gang of printing
devices, a pod, a substrate and a positioner, wherein: the pod
comprises a receptacle for reversibly attaching the gang, the
positioner moves the pod relative to the substrate, each of the
printing devices comprises a reservoir containing a different,
predetermined agent unique to the reservoir and in fluid connection
with the reservoir, a capillary having proximal and distal openings
open to ambient pressure and a printing tip comprising the distal
opening and which prints the agent on the substrate, the gang
comprises a nozzle surface from which protrudes a plurality of
nozzles, each having a proximal and a distal end, wherein the
distal end comprises the printing tip, and the system prints by
decelerating the capillaries to move the agent through the bores,
out the tips and onto the substrate.
2. A printing system according to claim 1, wherein the nozzle
surface has a flatness variation of less than 1 um.
3. A printing system according to claim 1, wherein the nozzle
surface has an internozzle distance variation of less than 1%.
4. A printing system according to claim 1, wherein the nozzles are
spaced to correspond with a predetermined desired array
density.
5. A printing system according to claim 1, wherein the nozzles are
spaced to correspond with a predetermined desired array density,
wherein the density is 9 mm center-to-center.
6. A printing system according to claim 1, wherein the gang is
fabricated from a single block of material.
7. A printing system according to claim 1, wherein the gang is made
by injection molding, embossing or etching.
8. A printing system according to claim 1, wherein the gang is made
of a plastic.
9. A printing system according to claim 1, wherein the gang is made
of a plastic selected from the group consisting of polycarbonate,
polystyrene, polypropylene and PMMA.
10. A printing system according to claim 1, wherein the gang is
made of a glass or ceramic.
11 A printing system according to claim 1, wherein the gang is made
of a semiconductor.
12. A printing system according to claim 1, wherein the gang is
made of a semiconductor and the semiconductor is silicon.
13. A printing system according to claim 1, wherein the gang is
made of metal.
14. A printing system according to claim 1, wherein the gang is
made of metal and the metal is stainless steel.
15. A printing system according to claim 1, wherein the agent is a
polypeptide or a polynucleotide.
16. A printing system according to claim 1, wherein the agent is a
polynucleotide at least 50 nucleotides in length.
17. A printing system according to claim 1, wherein the bore tapers
toward the distal opening of the tip.
18. A printing system according to claim 1, wherein the substrate
is selected from the group consisting of glass, ceramic, plastic,
metal, silicon, acetate and cellulose.
19. A printing system according to claim 1, wherein the substrate
provides a homogeneous surface.
20. A printing system according to claim 1, wherein the substrate
provides a surface offering differential surface chemistry or
topography.
21. A printing system according to claim 1, wherein the substrate
provides a surface offering differential surface chemistry or
topography, which provide predetermined printing sites adapted to
receiving binding, reacting, containing or retaining the agent or
liquid.
22. A printing system according to claim 1, wherein each printing
device further comprises a non-capillary chamber also containing
the liquid and having a relatively larger internal diameter than
and in fluid connection with the capillary.
23. A printing system according to claim 1 further comprising a
motion resistor operatively joined to the capillary and providing
an incomplete resistance to motion of the capillary along its
longitudinal axis, biasing said motion toward the substrate,
wherein the resistor is selected from a plurality of springs, an
elastomeric membrane and the weight of the capillary.
24. A printing system according to claim 1 further comprising a
motion resistor operatively joined to the capillary and providing
an incomplete resistance to motion of the capillary along its
longitudinal axis, biasing said motion toward the substrate,
wherein the resistor is the weight of the capillary.
25. A printing system according to claim 1 further comprising a
register comprising a guide which contacts a registration portion
of each printing device, distal to the attachment portion, and
moves the tip relative to the substrate.
26. A printing system according to claim 1, further comprising a
preservation device within, containing or in contact with each
printing device, which preserves the capability of the printing
device to print the agent on the substrate over long-term storage
of the printing device, wherein the preservation device comprises a
deterrent to evaporation of the liquid, wherein the deterrent is
selected from the group consisting of a hermetic barrier, a
refrigerator, a humidifier and a hygroscopic agent.
27. A printing system according to claim 1, further comprising a
preservation device within, containing or in contact with each
printing device, which preserves the capability of the printing
device to print the agent on the substrate over long-term storage
of the printing device, wherein the preservation device comprises a
deterrent to evaporation of the liquid, wherein the deterrent is a
hermetic barrier.
28. A method for printing an agent on a substrate comprising the
step of printing an agent with the printing system of claim 1 by
decelerating the capillary to move the agent through the bore, out
the tip and onto the substrate.
29. A method for printing an agent on a substrate comprising the
step of printing an agent with the printing system of claim 6 by
decelerating the capillary to move the agent through the bore, out
the tip and onto the substrate.
30. A method for printing an agent on a substrate comprising the
step of printing an agent with the printing system of claim 7 by
decelerating the capillary to move the agent through the bore, out
the tip and onto the substrate.
31. A method for printing an agent on a substrate comprising the
step of printing an agent with the printing system of claim 8 by
decelerating the capillary to move the agent through the bore, out
the tip and onto the substrate.
32. A method for printing an agent on a substrate comprising the
step of printing an agent with the printing system of claim 10 by
decelerating the capillary to move the agent through the bore, out
the tip and onto the substrate.
33. A method for printing an agent on a substrate comprising the
step of printing an agent with the printing system of claim 11 by
decelerating the capillary to move the agent through the bore, out
the tip and onto the substrate.
34. A method for printing an agent on a substrate comprising the
step of printing an agent with the printing system of claim 13 by
decelerating the capillary to move the agent through the bore, out
the tip and onto the substrate.
35. A method for printing an agent on a substrate comprising the
step of printing an agent with the printing system of claim 16 by
decelerating the capillary to move the agent through the bore, out
the tip and onto the substrate.
36. A method for printing an agent on a substrate comprising the
step of printing an agent with the printing system of claim 19 by
decelerating the capillary to move the agent through the bore, out
the tip and onto the substrate.
37. A method for printing an agent on a substrate comprising the
step of printing an agent with the printing system of claim 22 by
decelerating the capillary to move the agent through the bore, out
the tip and onto the substrate.
38. A method for printing an agent on a substrate comprising the
step of printing an agent with the printing system of claim 23 by
decelerating the capillary to move the agent through the bore, out
the tip and onto the substrate.
39. A method for printing an agent on a substrate comprising the
step of printing an agent with the printing system of claim 25 by
decelerating the capillary to move the agent through the bore, out
the tip and onto the substrate.
Description
INTRODUCTION
[0001] 1. Field of the Invention
[0002] The invention is in the field of capillary printing systems
and their fabrication.
[0003] 2. Background
[0004] 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. W095/35505 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.RTM. DNA Workstation by Hamilton Co., Reno NV; 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
[0005] 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.
[0006] 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.
[0007] 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.
[0008] 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.
[0009] 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.
[0010] 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.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] FIG. 1 shows a schematic of a printing head providing a
ganged plurality of printing devices.
[0012] FIG. 2 shows a schematic of a spring block motion resistor,
a printing head and a registration plate.
[0013] FIG. 3 shows a schematic of a single printing device in the
context of spring block motion resistor, printing head and
registration plate portions.
[0014] FIG. 4 shows a schematic of a plurality of printing devices
in the context of block motion resistor, elastomeric sheet and
printing head portions.
[0015] FIG. 5 shows a schematic of a single printing device in the
context of foam plug spring block motion resistor and printing head
portions.
[0016] FIG. 6 shows a schematic of an inserted capillary printing
device and a machined in printing device in the context of
plunger-bearing spring block motion resistor and printing head
portions.
[0017] FIG. 7 shows a schematic of a printing head portion having
compressable channel walls.
[0018] FIG. 8 shows a schematic of a single-piece construction low
density multi-chanel printing head.
[0019] FIG. 9 shows a schematic of a single-piece construction high
density multi-chanel printing head.
[0020] FIG. 10 shows schematic of a registration plate and a
printing head comprising a floppy door preservation device.
[0021] FIG. 11 shows schematic of a registration plate housing a
printing head comprising a floppy door preservation device with the
door opened.
[0022] FIG. 12 shows a schematic of an open jewel box type
preservation device housing a printing head.
[0023] FIG. 13 shows a schematic of a closed caddy box type
preservation device housing a printing head.
[0024] FIG. 14 shows a schematic of an open caddy box type
preservation device housing a printing head.
[0025] FIG. 15 shows a schematic of a spring block and an open
pop-out box type preservation device housing a printing head.
[0026] 15 FIG. 16 shows a schematic of a spring block depressing
the printing head of an open pop-out box type preservation
device.
[0027] FIG. 17 shows a schematic of a open, passive loading, vaccum
evacuation printing tip system.
[0028] FIG. 18 shows a schematic of a valve-actuated, passive
loading, vaccum evacuation, presure purging printing tip
system.
[0029] FIG. 19 shows a schematic of a valve-actuated, active
loading, vaccum evacuation, presure purging printing tip
system.
[0030] FIG. 20 shows a schematic of a gravity or pressure loading,
active purging printing tip system.
[0031] FIG. 21 shows a schematic of a high-throughput a printing
system.
DETAILED DESCRIPTION OF PARTICULAR EMBODIMENTS OF THE INVENTION
[0032] The following descriptions of particular embodiments and
examples are offered by way of illustration and not by way of
limitation.
[0033] In a first aspect, 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. This system is specifically
adapted for long-term storage of the printing device and is
amenable to a wide variety of suitable pods, detachable printing
devices, substrates, positioners, preservation devices,
applications and more particular embodiments.
[0034] Suitable pods include any structural member that transfers
the positioning of the positioner to the printing device through a
receptacle for reversibly attaching an attachment portion of the
printing device. For example, the pod may simply be the terminus of
a mechanical arm of the positioner with an engaging recess for
receiving the proximal (distal from the tip) end of a capillary
printing device.
[0035] Suitable printing devices include any structural member
which combines by fluid connection the requisite reservoir and
capillary. For example, the printing device may simply be a
capillary comprising a liquid-filled bore having a proximate
reservoir portion and terminating at a distal portion comprising
the printing tip. Alternatively, the reservoir may comprise a more
voluminous non-capillary liquid filled chamber having a relatively
larger internal diameter in fluid connection with a capillary
comprising the printing tip. The reservoir portion of the printing
device is adapted to contain and contains a liquid comprising a
predetermined agent. The device may be made of any convenient and
compatible material. For example, suitable capillary fabrication
material ceramic, silicons, glasses, etc. The printing device is
adapted or adaptable to contain, store and/or print a wide variety
of liquids, including aqueous liquids, liquids comprising organic
polar solvents such as alcohols, DMSO, acetonitrile, etc. nonpolar
solvents such benzene, chloroform, etc.
[0036] Suitable substrates include any material providing a
suitable printing surface, and include sheets of glasses, ceramics,
plastics, metals, silicons, acetate, cellulose (paper), etc. The
substrate may provide a homogeneous surface or a surface offering
differential surface chemistry, topography, etc. For example, the
surface may offer predetermined printing sites adapted to
receiving, binding, reacting, containing and/or retaining the
printing fluid.
[0037] Suitable positioners include any device which provides the
requisite positioning of the printing device to effect the desired
printing sites on the substrate. Frequently, the positioner will
provide a first positioning within the two-dimensional plane of the
substrate surface and a second positioning perpendicular to the
surface to effect contact printing on the surface. The positioner
is generally electomechanically operated by a computer controlled
robot.
[0038] Generally, the preservation device of these systems provides
a deterrent to evaporation of the liquid, such that printing can be
interrupted for extended periods, such as days, preferably weeks,
more preferably months and even years, and then resumed without
reloading the printing device. In various embodiments, the systems
suffer less than a 50%, preferably less than a 20%, more preferably
less than a 5% degradation in printing capacity over the storage
period, as measured by subsequent error or misprint frequency,
fluid loss, etc., as compared with an otherwise comparable but
uninterrupted system. A wide variety of suitable preservation
devices may be used. In one example, the device comprises a
hermetic barrier, such as a seal on the printing device or a
container capable of receiving and housing the printing device,
which provides a system that is relatively, preferably
substantially, more preferably fully closed to the printing solvent
liquid and vapor. These barrier or containment devices may also
provide a solvent vapor distributor, such as an absorbent sponge
wetted with the solvent of the printing fluid, within the closed
system to further minimize evaporation. In another example, the
device comprises a refrigerator to cool or preferably freeze the
liquid in the capillary of the printing device. In yet another
example, the device comprises a hygroscopic agent which is
incorporated in the liquid in the capillary and reduces the
volatility of the liquid. For example, where the solvent of the
liquid is water, suitable agents include glycerol (e.g. 5-95%),
salts, etc.
[0039] The printing system is adaptable to virtually any
application of small volume, high resolution liquid printing. For
example, a wide variety of chemical and biochemical libraries may
be deposited, including libraries derived from random or directed
synthetic schemes, natural products including genetic material,
etc. A particular application is the deposition of high density
arrays of biochemical reagents or analytes such as polypeptides and
polynucleotides (polymers of amino acids and nucleotides,
preferably at least 5, more preferably at least 15, more preferably
at least 50, more preferably at least 150 monomer units in length),
e.g. for effecting solid phase, preferably high throughput solid
phase immuno assays and hybridization assays.
[0040] More particular embodiments of this system include systems
wherein the dimensions and composition of the printing device
capillary bore interact with the fluid contained therein to
maintain the fluid proximate to the distal opening of the capillary
tip. For example, the capillary bore may be tapered, preferably
conically tapered toward the distal opening of the tip.
[0041] In another more particular embodiment, 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.
Such a motion resistor is especially important to facilitate
contact printing on relatively planar or flat surfaces, especially
wherein the system comprises a plurality of printing devices which
print in concert, wherein the resistor(s) permit simultaneous
contact of the printing devices on the surface.
[0042] In another more particular embodiment, the printing device
is of one-piece construction and/or comprises a wire bonding
capillary, described below. The system may also comprise a
detachable ganged plurality of printing devices.
[0043] In another more particular embodiment, 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. A wide variety of registers are provided. A printing system
comprising a register may further comprise first and second
detachable printing capillaries comprising respective first and
second probes, a pod comprising a receptacle for attaching one of
the capillaries, a substrate upon which the capillaries deposit the
probes, whereupon detachment of the first capillary and attachment
of the second capillary after deposition of a first portion of a
high density probe array by the first capillary on the substrate,
the register is capable of positioning the second capillary at a
sufficiently similar position relative to the substrate to permit
deposition of a second portion of the array by the second capillary
on the substrate. In this system, the capillaries and probes may be
different or the same.
[0044] In a second aspect, 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. This system provides a wide variety of
ways of ganging a plurality of printing devices. In one embodiment,
the detachable ganged plurality comprises a block having
receptacles or holes for and which laterally constrain each of the
printing devices. Alternatively, a rigid or elastomeric band or
clamp may be used to gang together the printing devices. In a
preferred embodiment, these systems provide analyte-specific
dedicated printing devices.
[0045] In another embodiment of this aspect of the invention, a
one-piece block fabricated from a single material element provides
the detachable ganged plurality, increasing the precision,
accuracy, repeatability, reliability, speed and permitted densities
of spot deposition. Because it is made from a single material
element this device is also easier and less expensive to construct
and maintain. A wide variety of standard microlithography,
micromachining and/or microfabrication methods known to those in
the art may be used to construct these devices including injection
molding, embossing, etching methods such as deep reaction ionic
etching (DRIE), electric discharge machining (EDM), deposition,
computer numerical control (CNC) milling, etc. Accordingly, the
devices may be manufactured from a wide variety of materials
depending on the selected manufacturing method, including plastics
such as polycarbonate, polystyrene, polypropylene and PMMA; glasses
and/or ceramics; semiconductor material such as silicon; and metals
such as stainless steel. The devices may be constructed in a
variety formats in terms of nozzle density, head size, reservoir
size, etc. Print precision and accuracy are provided by precision
engineering specifications including: nozzle surface (e.g.
flatness) variation of less than 10, preferably less than 5, more
preferably less than 2, more preferably less than 1 um across all
the nozzle tips of a head and internozzle print volume and distance
(center-to-center) variation of less than about 4, preferably less
than about 2, more preferably less than 1, more preferably less
than 0.5%. The nozzles may be spaced to provide direct loading from
standard microtiter sample plates (e.g. 9 mm center-to-center) or
at higher densities wherein the reservoirs may be loaded with
conventional microvolume liquid handling devices. In a particular
embodiment, the nozzles are spaced to correspond with the desired
array density, avoiding the need for off-set printing.
[0046] In a third aspect, 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. Wire bonding capillaries
are adapted from semiconductor manufacturing, where a wire bonding
process is used to electrically connect metal bond pads formed on a
semiconductor die to the leadfingers of a leadframe. In this
process, a bond wire is threaded through a wire bonding capillary
and the end of the wire protruding through the capillary tip is
heated to a molten ball. The molten ball is then mechanically
pressed by the bonding capillary against the heated bond pad to
alloy the metallic elements of the wire and bond pad. The capillary
is then moved to a bonding site on the designated leadfinger where
the wire is pressed against the heated leadfinger to bond the wire,
then tensioned and sheared. Wire bonding capillaries are well known
in the semiconductor manufacturing art, are the subject of numerous
publications and patents (see e.g. U.S. Pat Nos. 3,894,671;
4,877,173; 5,082,154; 5,558,270; 5,662,261) and are commercially
available from a number of sources (e.g. Micro-Swiss of Kulicke
& Soffa Industries, Inc., Willow Grove Pa.; Gaiser Tool
Company, Ventura, Calif.; Small Precision Tools, Petaluma, Calif.,
etc.) 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.
[0047] 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 contact printing, e.g. tapping the tip onto the
substrate. A wide variety of methods may be used for loading and/or
unloading the printing devices, including passive capillary loading
and unloading from the printing tip, vacuum-assisted unloading,
active pressure purging, etc. Uninterrupted mult-head printing
systems comprising 25 20.times.20 (400 nozzle) heads provide for
offset printing 10,000 spot arrays on chip substrates at rates of
at least 0.2 chips/sec., preferably 1 chip/sec., more preferably at
least 5 chips/sec.
EXAMPLES
[0048] Referring to FIG. 1, a plurality of printing devices 11 are
shown housed in receptacles of a gang 12 comprising tabs 13 for
attaching to a pod (not shown) of a printing system.
[0049] Referring to FIG. 2, a plurality of printing devices 11 are
shown housed in receptacles of a gang print head 12 comprising tabs
13. Above the print head 12 is a spring block 21 retaining a
plurality of vertical actuators 22. Below the print head 12 is a
registration plate 23 comprising a plurality of registration
apertures 24.
[0050] Referring to FIG. 3, a printing device 11 is shown housed in
a receptacle of a portion of a print head 12. Above the portion of
the print head 12 is a portion of a spring block 21 is shown
retaining a vertical actuators 22 comprising a spring 31, a spring
shaft 32 comprising a vent 33. Below the portion of the print head
12 is a portion of the registration plate 23 comprising a
registration aperture 24.
[0051] Referring to FIG. 4, a plurality of printing devices 11 are
shown housed in receptacles of a portion of a print head 12. Above
the portion of the print head 12 is a spring and vent cavity block
41 and between the block 41 and the print head 12 is a punch vented
latex spring sheet 42.
[0052] Referring to FIG. 5, a printing device 11 is shown housed in
a receptacle of a portion of a print head 12. Above the portion of
the print head 12 is a portion of a spring and vent cavity block 41
is shown retaining a quick-recovery open cell foam spring/vent
combination 51.
[0053] Referring to FIG. 6, an inserted capillary printing device
61 and a machined in printing device 62 are shown housed and
formed, respectively, in receptacles of a portion of a print head
12. Above the portion of the print head 12 is a spring block 63.
The spring block 63 contains spring-loaded plungers 64, each
comprising a spring 65, a flange 66 and a shaft 67, and positioned
above the printing devices 61 and 62.
[0054] Referring to FIG. 7, a plurality of machined in printing
devices 62 are shown formed in receptacles of a portion of a print
head 12, wherin the capillary portion 71 of the devices 62 have
compressible channel walls 72.
[0055] Referring to FIG. 8, a single-piece construction low density
(e.g. 64 tips/cm.sup.2) multi-chanel printing head 81 is shown in
cross-section. The head 81 comprises injection molded reservoirs 82
in fluid connection with the capillary bores 83 of molded printing
tips 84.
[0056] Referring to FIG. 9, a single-piece construction high
density (e.g. 400 tips/cm.sup.2) multi-chanel printing head 91 is
shown in cross-section. The head 91 comprises etched reservoirs 92
in fluid connection with the capillary bores 93 of etched printing
tips 94.
[0057] Referring to FIG. 10, a print head 12 with an operatively
affixed closed floppy door preservation device 101 is shown in
approach toward a registration plate 102 comprising a plurality of
printing tip registration apertures 103.
[0058] Refering to FIG. 11, a print head 12 with an operatively
affixed open floppy door preservation device 101 is shown in
contact with a registration plate 102 comprising a plurality of
printing tip registration apertures 103, wherein the open floppy
door preservation device 101 is shown in a slide open orientation.
In an alternative embodiment, the open floppy door preservation
device 101 may be swung open.
[0059] Referring to FIG. 12, an open jewel box type preservation
device 121 containing a saturated foam pad 122 is shown housing a
print head 12.
[0060] Referring to FIG. 13, a closed caddy box type preservation
device 131 containing a saturated foam pad 122 is shown housing a
print head 12.
[0061] Referring to FIG. 14, an open caddy box type preservation
device 131 containing a saturated foam pad 122 is shown housing a
print head 12.
[0062] Referring to FIG. 15, a pop-out box type preservation device
151 containing a saturated foam pad is 122 shown in open position
housing a print head 12. Above and approaching the print head 12 is
shown a spring block 152.
[0063] Referring to FIG. 16, a pop-out box type preservation device
151 containing a saturated foam pad is 122 shown in open position
housing a print head 12. Above and depressing the print head 12 is
shown a spring block 152.
[0064] Referring to FIG. 17, a printing device 11 comprising a vent
hole 171 is shown housed in a linear bearing receptacle of a
portion of a print head 12. Below the portion of the print head 12
is a portion of a vacuum plate 172 comprising a vacuum aperture
173.
[0065] Referring to FIG. 18, a printing device 11 is shown housed
in a linear bearing receptacle of a portion of a print head 12.
Below the portion of the print head 12 is a portion of a vacuum
plate 172 comprising a vacuum aperture 173. In fluid connection
with the printing device 11 through tubing 181 is a three-way valve
182 alternatively connecting the device to atmospheric pressure,
closure or pressurized nitrogen.
[0066] Referring to FIG. 19, a printing device 11 is shown housed
in a linear bearing receptacle of a portion of a print head 12.
Below the portion of the print head 12 is a portion of a vacuum
plate 172 comprising a vacuum aperture 173. In fluid connection
with the printing device 11 through tubing 181 is are four two-way
valves 191 parallel, alternatively connecting the device to closure
or respectively, pressurized nitrogen, water, atmospheric pressure
and vacuum.
[0067] Referring to FIG. 20, a printing device 11 is shown in fluid
connection through tubing 181 with a sample reservoir 201.
[0068] Referring to FIG. 21, a printing system 210 comprising a
multihead printing assembly 211 rotatably attached to a multichip
turntable 212. The assemby 211 comprises a plurality of
single-piece construction high density (400 tips/cm.sup.2)
multi-channel detachable printing heads 91 joined to the assembly
211 through actuators 213 which provide positioning stages 214 and
L-brackets 215 for attaching the print heads 91. The turntable 212
provides chip recepticles 217 which position the chips 216 which
provide a printing substrate. In operation, the actuators 213
simulateously stamp their respective printing heads 91 on the
corresponding chips 216. Thereafter, the turntable 212 rotates one
chip position and the necessary printing offset is effected by
turntable 212 rotation, acutator 213 positioning, or both. As the
printing on a given chip 216 is completed (e.g. a complete array is
deposited), the chip 216 is removed from the turntable 212 and
replaced with a new chip 216, thereby providing uninterrupted
printing.
[0069] All publications and patent applications cited in this
specification are herein incorporated by reference as if each
individual publication or patent application were specifically and
individually indicated to be incorporated by reference. Although
the foregoing invention has been described in some detail by way of
illustration and example for purposes of clarity of understanding,
it will be readily apparent to those of ordinary skill in the art
in light of the teachings of this invention that certain changes
and modifications may be made thereto without departing from the
spirit or scope of the appended claims.
* * * * *