U.S. patent application number 10/626627 was filed with the patent office on 2005-04-28 for compositions and methods involving direct write optical lithography.
This patent application is currently assigned to Affymetrix, Inc.. Invention is credited to Quate, Calvin F., Stern, David.
Application Number | 20050088722 10/626627 |
Document ID | / |
Family ID | 26776859 |
Filed Date | 2005-04-28 |
United States Patent
Application |
20050088722 |
Kind Code |
A1 |
Quate, Calvin F. ; et
al. |
April 28, 2005 |
Compositions and methods involving direct write optical
lithography
Abstract
An improved optical photolithography system and method provides
predetermined light patterns generated by a direct write system
without the use of photomasks. The Direct Write System provides
predetermined light patterns projected on the surface of a
substrate (e.g., a wafer) by using a computer controlled means for
dynamically generating the predetermined light pattern, e.g., a
spatial light modulator. Image patterns are stored in a computer
and through electronic control of the spatial light modulator
directly illuminate the wafer to define a portion of the polymer
array, rather than being defined by a pattern on a photomask. Thus,
in the Direct Write System each pixel is illuminated with an
optical beam of suitable intensity and the imaging (printing) of an
individual feature is determined by computer control of the spatial
light modulator at each photolithographic step without the use of a
photomask. The Direct Write System including a spatial light
modulator is particularly useful in the synthesis of DNA arrays and
provides an efficient means for polymer array synthesis by using
spatial light modulators to generate a predetermined light pattern
that defines the image patterns of a polymer array to be
deprotected.
Inventors: |
Quate, Calvin F.; (Stanford,
CA) ; Stern, David; (Mountain View, CA) |
Correspondence
Address: |
GREENBLUM & BERNSTEIN, P.L.C.
1950 ROLAND CLARKE PLACE
RESTON
VA
20191
US
|
Assignee: |
Affymetrix, Inc.
Santa Clara
CA
|
Family ID: |
26776859 |
Appl. No.: |
10/626627 |
Filed: |
July 25, 2003 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10626627 |
Jul 25, 2003 |
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10223719 |
Aug 20, 2002 |
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10223719 |
Aug 20, 2002 |
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09880058 |
Jun 14, 2001 |
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6480324 |
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09880058 |
Jun 14, 2001 |
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09318775 |
May 26, 1999 |
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6271957 |
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60087333 |
May 29, 1998 |
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Current U.S.
Class: |
359/298 |
Current CPC
Class: |
B01J 2219/00637
20130101; G03F 7/70283 20130101; G03F 7/70291 20130101; B01J
19/0046 20130101; B01J 2219/0059 20130101; B01J 2219/00608
20130101; B01J 2219/00722 20130101; B01J 2219/00439 20130101; B01J
2219/00527 20130101; B01J 2219/00596 20130101; B82Y 30/00 20130101;
C40B 60/14 20130101; B01J 2219/00689 20130101; B01J 2219/00529
20130101; C40B 40/06 20130101; B01J 2219/00659 20130101; B01J
2219/00626 20130101; B01J 2219/00725 20130101; B01J 2219/00605
20130101; B01J 2219/00711 20130101; B01J 2219/00617 20130101; B01J
2219/00612 20130101; B01J 2219/00585 20130101; G03F 7/704 20130101;
B01J 2219/00353 20130101 |
Class at
Publication: |
359/298 |
International
Class: |
G02F 001/29; G02B
026/08 |
Claims
1-112. (canceled)
113. A method of attaching monomers at specific reaction sites on a
substrate, said specific reaction sites containing one or more
non-photolabile protected initiating moieties, the method
comprising: a) contacting said substrate with a liquid solution
comprising one or more photo-reagent precursors, said precursors
selected from the group consisting of acid and base precursors,
such that said liquid solution is in contact with said initiating
moieties; b) isolating said specific reaction sites; c) irradiating
a selected number of the isolated reaction sites to produce, in
situ, at least one photo-generated reagent without the formation of
a polymeric coating layer, thereby directly deprotecting the
initiating moieties at the irradiated reaction sites so as to
create deprotected initiating moieties; and d) contacting said
substrate with a first monomer, said first monomer comprising an
unprotected reactive site and a protected reactive site, under
conditions such that said unprotected reactive site of said monomer
couples with said deprotected initiating moieties so as to create
an attached first monomer.
114. The method of claim 113, wherein said initiating moieties of
step (a) comprise linker molecules, each of said linker molecules
comprising a reactive functional group protected by an acid-labile
protecting group.
115. The method of claim 114, wherein said reactive functional
group of said linker molecules comprises a hydroxyl group.
116. The method of claim 113, wherein said first monomer is
selected from the group consisting of nucleophosphoramidites,
nucleophosphonates and analogs thereof.
117. The method of claim 113, wherein said attached first monomer
of step (d) comprises a nucleotide monomer with a protected
group.
118. The method of claim 117, wherein said protected group is
protected by an acid-labile group.
119. The method of claim 117, further comprising the step of
deprotecting said protected group so as to create a deprotected
attached nucleotide monomer.
120. The method of claim 119, further comprising the step of
contacting said deprotected attached nucleotide monomer with a
second monomer, said second monomer comprising an unprotected
reactive site and a protected reactive group, under conditions such
that said unprotected reactive site of said second monomer couples
with said deprotected attached nucleotide monomer so as to create
an attached second monomer, said attached first and second monomers
comprises a multimer.
121. The method of claim 120, wherein said multimer comprises
DNA.
122. The method of claim 1113, wherein said initiating moieties of
step (a) comprise oligomers to which a monomer can be attached.
123. An apparatus for generating a time and spatially dependent
light spectrum comprising: (a) a light source positioned to direct
a light output, wherein said light source comprises a light that is
redirected by a micromirror array under the control of a computer
to produce said light output; (b) a variable spectrum filter placed
in the path of the light redirected by said light source, wherein
said variable spectrum filter passes one or more spatially
separated wavelengths of light; and (c) said a computer controls
the relative position of said variable spectrum filter and said
light output.
124. The apparatus of claim 123, wherein said computer controls the
position of the variable spectrum filter in relation to the light
source, wherein the light passed by the variable spectrum filter is
time and wavelength controlled.
125. The apparatus of claim 123, wherein said one or more spatially
separated wavelengths of light are detected by a sensor that
produces an output signal and the output signal of said sensor is
directed to said computer, wherein said computer directs the
position of the variable spectrum signal and said light source
based on the output signal of said sensor.
126. The apparatus of claim 123, wherein said light output is a UV
light, visible or infrared light.
127. The apparatus of claim 123, further comprising one or more
lenses between said light source and a target, wherein one or more
lenses are further defined as a lens system that may change the
magnification of light in one or more dimensions reflected by said
light source.
128. The apparatus of claim 123, wherein said micromirror array is
further defined as a two-dimensional micromirror array.
129. The apparatus of claim 123, further comprising one or more
diffusion lenses between said light source and said micromirror
array.
130. The apparatus of claim 123, wherein said one or more
wavelengths of light catalyze a reaction involving a light
catalyzable compound proximate said target.
131. The apparatus of claim 123, further comprising: (a) a CCD
camera positioned to receive light from said target to measure the
intensity and wavelength of the light striking said target; and (b)
said computer connected to, controlling and receiving the output
from said CCD camera.
132. The apparatus of claim 123, wherein said light output is a
combination of UV light, visible and infrared light.
133. The apparatus of claim 123, wherein said one or more
wavelengths of light interact with said target to produce the
activation of one or more cellular functions at a site of the
target.
134. The apparatus of claim 123, wherein said one or more
wavelengths of light catalyze the activation of one or more
nucleotide bases at said target.
135. The apparatus of claim 123, wherein said one or more
wavelengths of light catalyze the activation of a light catalyzable
reaction involving one or more amino acid residue at said
target.
136. The apparatus of claim 123, wherein said one or more
wavelengths of light crosslink a molecule proximate said
target.
137. An apparatus for projecting one or more wavelengths of light
comprising: (a) a light source positioned to redirect light from
said light source toward a target, wherein said light source is
further defined as comprising a light that produces one or more
wavelengths of light that are redirected by a micromirror array
under the control of a computer to produce said light; (b) a
variable spectrum generator positioned to pass one or more
spatially separated wavelengths of light from said light source;
and (c) said computer connected to, and controlling, said light
source and said variable spectrum generator to pass one or more
wavelengths of light from said light source toward said target.
138. The apparatus of claim 137, wherein said computer can control
the position of the variable spectrum generator in relation to the
light source, wherein the light passed by the variable spectrum
generator is time and wavelength controlled.
139. The apparatus of claim 137, wherein said one or more
wavelengths of light are detected at a sensor that produced an
output signal and the output signal of said sensor is directed to
said computer, wherein said computer directs the position of the
variable spectrum generator and said light source based on the
output signal of said sensor.
140. The apparatus of claim 137, wherein said light that produces
one or more spatially separated wavelengths is a xenon lamp, or a
mercury lamp, or a laser or a combination thereof.
141. The apparatus of claim 137, further comprising a total
internal reflection mirror disposed in a position to redirect
output of said light.
142. The apparatus of claim 137, wherein said target is mounted and
illuminated on a movable platform that is controlled via said
computer to allow for multiple repetitive exposures of said target
to said one or more spatially separated wavelengths of light passed
by said variable spectrum generator.
Description
[0001] This application relates to provisional application Ser. No.
60/087,333 filed May 29, 1998 which is hereby incorporated by
reference in its entirety.
BACKGROUND OF THE INVENTION
[0002] 1. Technical Field of the Invention
[0003] This invention relates to optical lithography and more
particularly to direct write optical lithography.
[0004] 2. Description of the Related Art
[0005] Polymer arrays, such as the GeneChip.RTM. probe array
(Affymetrix, Inc., Santa Clara, Calif.), can be synthesized using
light-directed methods described, for example, in U.S. Pat. No.
Nos. 5,143,854; 5,424,186; 5,510,270; 5,800,992; 5,445,934;
5,744,305; 5,384,261 and 5,677,195 and PCT published application
no. WO 95/11995, which are hereby incorporated by reference in
their entireties. As an example, light-directed synthesis of
oligonucleotides employs 5'-protected nucleosidephosphoramidite
"building blocks." The 5'-protecting groups may be either
photolabile or acid-labile. A plurality of polymer sequences in
predefined regions are synthesized by repeated cycles of
deprotection (selective removal of the protective group) and
coupling. Coupling (i.e., nucleotide or monomer addition) occurs
only at sites that have been deprotected. Three methods of
light-directed synthesis are: use of photolabile protecting groups
and direct photodeprotection (DPD); use of acid-labile
4,4'-dimethoxytrityl (DMT) protecting groups and a photoresist; use
of DMT protecting groups and a polymer film that contains a
photoacid generator (PAG).
[0006] These methods have many process steps similar to those used
in semiconductor integrated circuit manufacturing. These methods
also often involve the use of photomasks (masks) that have a
predefined image pattern which permits the light used for synthesis
of the polymer arrays to reach certain regions of a substrate but
not others. The substrate can be non-porous, rigid, semi-rigid,
etc. It can be formed into a well, a trench, a flat surface, etc.
The substrate can include solids, such as siliceous substances such
as silicon, glass, fused silica, quartz, and other solids such as
plastics and polymers, such as polyacrylamide, polystyrene,
polycarbonate, etc. Typically, the solid substrate is called a
wafer from which individual chips are made (See the U.S. patents
above which are incorporated herein by reference). As such, the
pattern formed on the mask is projected onto the wafer to define
which portions of the wafer are to be deprotected and which regions
remain protected. See, for example, U.S. Pat. Nos. 5,593,839 and
5,571,639 which are hereby incorporated by reference in their
entireties.
[0007] The lithographic or photochemical steps in the synthesis of
nucleic acid arrays may be performed by contact printing or
proximity printing using photomasks. For example, an emulsion or
chrome-on-glass mask is placed in contact with the wafer, or nearly
in contact with the wafer, and the wafer is illuminated through the
mask by light having an appropriate wavelength. However, masks can
be costly to make and use and are capable of being damaged or
lost.
[0008] In many cases a different mask having a particular
predetermined image pattern is used for each separate photomasking
step, and synthesis of a wafer containing many chips requires a
plurality of photomasking steps with different image patterns. For
example, synthesis of an array of 20 mers typically requires
approximately seventy photolithographic steps and related unique
photomasks. So, using present photolithographic systems and
methods, a plurality of different image pattern masks must be
pre-generated and changed in the photolithographic system at each
photomasking step. This plurality of different pattern masks adds
lead time to the process and complexity and inefficiency to the
photolithographic system and method. Further, contact printing
using a mask can cause defects on the wafer so that some of the
reaction sites are rendered defective. Thus, a photolithographic
system and method that does not require such masks and obviates
such difficulties would be generally useful in providing a more
efficient and simplified lithographic process.
SUMMARY OF THE INVENTION
[0009] In view of the above, one advantage of the invention is
providing an improved and simplified system and method for optical
lithography.
[0010] Another advantage of the present invention is providing an
optical lithography system and method that dynamically generates an
image using a computer and reconfigurable light modulator.
[0011] A further advantage of the present invention is providing an
optical lithography system and method that does not use
photomasks.
[0012] A still further advantage of the present invention is
providing an optical lithography system and method that uses
computer generated electronic control signals and a spatial light
modulator, without any photomask, to project a predetermined light
pattern onto a surface of a substrate for the purposes of
deprotecting various areas of a polymer array.
[0013] According to one aspect of the invention, polymer array
synthesis is performed using a system without photomasks.
[0014] According to a second aspect of the invention, polymer array
synthesis is performed using a system with a transmissive spatial
light modulator and without a lens and photomask.
[0015] According to another aspect of the invention, a Direct Write
System transmits image patterns to be formed on the surface of a
substrate (e.g., a wafer). The image patterns are stored in a
computer. The Direct Write System projects light patterns generated
from the image patterns onto a surface of the substrate for
light-directed polymer synthesis (e.g., oligonucleotide). The light
patterns are generated by a spatial light modulator controlled by a
computer, rather than being defined by a pattern on a photomask.
Thus, in the Direct Write System each pixel is illuminated with an
optical beam of suitable intensity and the imaging (printing) of an
individual feature on a substrate is determined dynamically by
computer control.
[0016] According to a further aspect of the invention, polymer
array synthesis is accomplished using a class of devices known as
spatial light modulators to define the image pattern of the polymer
array to be deprotected.
[0017] An even further aspect of the present invention provides
methods for synthesizing polymer arrays using spatial light
modulators and the polymer arrays synthesized using the methods
taught herein.
[0018] As can be appreciated by one skilled in the art, the
invention is relevant to optical lithography in general, and more
specifically to optical lithography for polymer array synthesis
using photolithograpic processes. However, it is inherent that the
invention is generally applicable to eliminating the need for a
photomask in optical lithography.
BRIEF DESCRIPTION OF THE DRAWINGS
[0019] The above objects, features, and advantages of the present
invention will become more apparent from the following detailed
description taken with the accompanying drawings in which:
[0020] FIG. 1 shows a first embodiment of the invention having a
light source, a reflective spatial light modulator, such as a
micro-mirror array, and a lens.
[0021] FIG. 2 is a diagrammatic representation of a second
embodiment of the invention employing an array of, for example,
micro-lenses.
[0022] FIG. 3 illustrates a micro-lens array in the form of Fresnel
Zone Plates, which may be used in the invention.
[0023] FIG. 4 shows a third embodiment of the invention having a
transmissive spatial light modulator.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0024] The present invention refers to articles and patents that
contain useful supplementary information. These references are
hereby incorporated by reference in their entireties.
[0025] The presently preferred invention is based on the principle
that a Direct Write Optical Lithography System will significantly
improve the cost, quality, and efficiency of polymer array
synthesis by providing a maskless optical lithography system and
method where predetermined image patterns can be dynamically
changed during photolithographic processing. As such, an optical
lithography system is provided to include a means for dynamically
changing an intended image pattern without using a photomask. One
such means includes a spatial light modulator that is
electronically controlled by a computer to generate unique
predetermined image patterns at each photolithograpic step in
polymer array synthesis. The spatial light modulators can be, for
example, micromachined mechanical modulators or microelectronic
devices (e.g. liquid crystal display (LCD)). The Direct Write
System of the present invention using such spatial light modulators
is particularly useful in the synthesis of polymer arrays, such as
polypeptide, carbohydrate, and nucleic acid arrays. Nucleic acid
arrays typically include polynucleotides or oligonucleotides
attached to glass, for example, Deoxyribonucleic Acid (DNA)
arrays.
[0026] Certain preferred embodiments of the invention involve use
of the micromachined mechanical modulators to direct the light to
predetermined regions (i.e., known areas on a substrate predefined
prior to photolithography processing) of the substrate on which the
polymers are being synthesized. The predetermined regions of the
substrate associated with, for example, one segment (referred to
herein as a pixel) of a micromachined mechanical modulator (e.g., a
micro-mirror array) are referred to herein as features. In each
predetermined region or feature a particular oligonucleotide
sequence, for example, is synthesized. The mechanical modulators
come in a variety of types, two of which will be discussed in some
detail below.
[0027] One type of mechanical modulator is a micro-mirror array
which uses small metal mirrors to selectively reflect a light beam
to particular individual features; thus causing the individual
features to selectively receive light from a light source (i.e.,
turning light on and off of the individual features). An example is
the programmable micro-mirror array Digital Micromirror Device
(DMD.TM.) manufactured by Texas Instruments, Inc., Dallas, Tex.,
USA. Texas Instruments markets the arrays primarily for projection
display applications (e.g., big-screen video) in which a highly
magnified image of the array is projected onto a wall or screen.
The present invention shows, however, that with appropriate optics
and an appropriate light source, a progranmable micro-mirror array
can be used for photolithographic synthesis, and in particular for
polymer array synthesis.
[0028] The Texas Instruments' DMD.TM. array consists of
640.times.480 mirrors (the VGA version) or 800.times.600 mirrors
(the super VGA (SVGA) version). Devices with more mirrors are under
development. Each mirror is 16 .mu.m.times.16 .mu.m and there are
1-.mu.m gaps between mirrors. The array is designed to be
illuminated 20 degrees off axis. Each mirror can be turned on
(tilted 10 degrees in one direction) or off (tilted 10 degrees in
the other direction). A lens (on axis) images the array onto a
target. When a micro-mirror is turned on, light reflected by the
micro-mirror passes through the lens and the image of the
micro-mirror appears bright. When a micro-mirror is turned off,
light reflected by the micro-mirror misses the lens and the image
of the micro-mirror appears dark. The array can be reconfigured by
software (i.e., every micro-mirror in the array can be turned on or
off as desired) in a fraction of a second.
[0029] An optical lithography system including a micro-mirror array
1 based spatial light modulator according to one embodiment of the
invention is shown in FIG. 1. This embodiment includes a spatial
light modulator made of a micro-mirror array 1, and arc lamp 3, and
a lens 2 to project a predetermined image pattern on a chip or
wafer (containing many chips) 4. In operation, collimated, filtered
and homogenized light 5 from the arc lamp 3 is selectively
reflected as a light beam 6 according to dynamically turned on
micro mirrors in the micro-mirror array 1 and transmitted through
lens 2 on to chip or wafer 4 as reflected light beam 8. Reflected
light from micro-mirrors that are turned off 7 is reflected in a
direction away from the lens 2 so that these areas appear dark to
the lens 2 and chip or wafer 4. Thus, the spatial light modulator,
micro-mirror array 1, modulates the direction of reflected light (6
and 7) so as to define a predetermined light image 8 projected onto
the chip or wafer 4. The direction of the reflected light alters
the light intensity transmitted from each pixel to each feature. In
essence, the spatial light modulator operates as a directional and
intensity modulator.
[0030] The micro-mirror array 1 can be provided by, for example,
the micro-mirror array of the Texas Instruments(TI) DMD, in
particular, the TI "SVGA DLP.TM." subsystem. The Texas Instruments
"SVGA DLP.TM." subsystem with optics may be modified for use in the
present invention. The Texas Instruments "SVGA DLP.TM." subsystem
includes a micro-mirror array (shown as micro-mirror array 1 in
FIG. 1), a light source, a color filter wheel, a projection lens,
and electronics for driving the array and interfacing to a
computer. The color filter wheel is replaced with a bandpass filter
having, for example, a bandpass wavelength of 365-410 nm
(wavelength dependent upon the type of photochemicals selected for
used in the process). For additional brightness at wavelengths of,
for example, 400-410 run, the light source can be replaced with arc
lamp 3 and appropriate homogenizing and collimating optics. The
lens included with the device is intended for use at very large
conjugate ratios and is replaced with lens 2 or set of lenses
appropriate for imaging the micro-mirror array 1 onto chip or wafer
4 with the desired magnification. Selection of the appropriate lens
and bandpass filter is dependent on, among other things, the
requisite image size to be formed on the chip, the type of spatial
light modulator, the type of light source, and the type of
photoresist and photochemicals being used in the system and
process.
[0031] A symmetric lens system (e.g., lenses arranged by type
A-B-C-C-B-A) used at 1:1 magnification (object size is the same as
the image size) is desirable because certain aberrations
(distortion, lateral color, coma) are minimized by symmetry.
Further, a symmetric lens system results in a relatively simple
lens design because there are only half as many variables as in an
asymmetric system having the same number of surfaces. However, at
1:1 magnification the likely maximum possible chip size is 10.88
mm.times.8.16 mm with a VGA device, or 10.2 mm.times.13.6 mm with
an SVGA device. Synthesis of, for example, a standard GeneChip.RTM.
12.8 mm.times.12.8 mm chip uses an asymmetric optical system (e.g.,
a magnification of about 1.25:1 with SVGA device) or a larger
micro-mirror array (e.g., 1028.times.768 mirrors) if the mirror
size is constant. In essence, the lens magnification can be greater
than or less than 1 depending on the desired size of the chip.
[0032] In certain applications of the invention, a relatively
simple lens system, such as a back-to-back pair of achromats or
camera lens, is adequate. A particularly useful lens for +some
applications of the invention is the Rodenstock (Rockford, Ill.)
Apo-Rodagon D. This lens is optimized for 1:1 imaging and gives
good performance at magnifications up to about 1.3:1. Similar
lenses may be available from other manufacturers. With such lenses,
either the Airy disk diameter or the blur circle diameter will be
rather large (maybe 10 um or larger). See Modern Optical
Engineering, 2d Edition, Smith, W. J., ed., McGraw-Hill, Inc., New
York (1990). For higher quality synthesis, the feature size is
several times larger than the Airy disk or blur circle. Therefore,
a custom-made lens with resolution of about 1-2 um over a 12.8
mm.times.12.8 mm field is particularly desirable.
[0033] A preferred embodiment of synthesizing polymer arrays with a
programmable micro-mirror array using the DMT process with
photoresist takes place as follows. First, a computer file is
generated and specifies, for each photolithography step, which
mirrors in the micro-mirror array 1 need to be on and which need to
be off to generate a particular predetermined image pattern. Next,
the individual chip or the wafer from which it is made 4 is coated
with photoresist on the synthesis surface and is mounted in a
holder or flow cell (not shown) on the photolithography apparatus
so that the synthesis surface is in the plane where the image of
the micro-mirror array 1 will be formed. The photoresist may be
either positive or negative thus allowing deprotection at locations
exposed to the light or deprotection at locations not exposed to
the light, respectively (example photoresists include: negative
tone SU-8 epoxy resin (Shell Chemical) and those shown in the above
cited patents and U.S. patent application Ser. No. 08/634,053). A
mechanism for aligning and focusing the chip or wafer is provided,
such as a x-y translation stage. Then, the micro-mirror array 1 is
programmed for the appropriate configuration according to the
desired predetermined image pattern, a shutter in the arc lamp 3 is
opened, the chip or wafer 4 is illuminated for the desired amount
of time, and the shutter is closed. If a wafer (rather than a chip)
is being synthesized; a stepping-motor-driven translation stage
moves the wafer by a distance equal to the desired center-to-center
distance between chips and the shutter of the arc lamp 3 is opened
and closed again, these two steps being repeated until each chip of
the wafer has been exposed.
[0034] Next, the photoresist is developed and etched. Exposure of
the wafer 4 to acid then cleaves the DMT protecting groups from
regions of the wafer where the photoresist has been removed. The
remaining photoresist is then stripped. Then DMT-protected
nucleotides containing the desired base (adenine (A), cytosine (C),
guanine (G), or thymine (T)) are coupled to the deprotected
oligonucleotides.
[0035] Subsequently, the chip or wafer 4 is re-coated with
photoresist. The steps from mounting the photoresist coated chip or
wafer 4 in a holder through re-coating the chip or wafer 4 with
photoresist are repeated until the polymer array synthesis is
complete.
[0036] It is worth noting that if a DPD method, using for example
1-(6-nitro-1,3-benzodioxol-5-yl)ethyloxycarbonyl (MeNPOC)
chemistry, or a PAG method, using a polymer film containing a
photoacid generator (PAG), are used for polymer array synthesis
then photoresist would not be used and the process is somewhat
simplified. However, the use of a direct write optical lithography
system with a spatial light modulator is also applicable to
performing a process of deprotection of reaction sites using the
DPD and PAG methods without photoresist.
[0037] As is clear from the above described method for polymer
array synthesis, no photomasks are needed. This simplifies the
process by eliminating processing time associated with changing
masks in the optical lithography system and reduces the
manufacturing cost for polymer array synthesis by eliminating the
cost of the masks as well as processing defects associated with
using masks. In addition, the process has improved flexibility
because reprogramming the optical lithography system to produce a
different generate and verify new photomasks, thus making it
possible to transfer an image pattern computer file directly from a
CAD or similar system to the optical lithography system or
providing electronic signals directly from the CAD system to drive
the optical lithography system's means for dynamically producing
the desired light pattern (e.g., spatial light modulator).
Therefore, the optical lithography system is simplified and more
efficient than conventional photomask based optical lithography
systems. This is particularly valuable in complex multiple step
photolithography processing; for example polymer array synthesis of
GeneChip.RTM. probe arrays having upwards of seventy or more
cycles, especially when many different products are made and
revised.
[0038] As indicated above, substrates coated with photoresist are
employed in preferred embodiments of the invention, e.g., using the
DMT process with photoresist. The use of photoresist with
photolithographic methods for fabricating polymer arrays is
discussed in McGall et al., Chemtech, pp. 22-32 (February 1997);
McGall et al., Proc. Natl. Acad. Sci., U.S.A., Vol. 93, pp.
13555-135.sup.60 (November 1996) and various patents cited above,
all of which are incorporated by reference in their entireties.
Alternatively, polymer array synthesis processing can be performed
using photoacid generators without using a conventional
photoresist, e.g., using the PAG process, or using direct
photodeprotection without using any photoresist, e.g., using the
DPD process. The use of photoacid generators is taught in U.S.
application Ser. No. 08/969,227, filed Nov. 13, 1997. However, the
present invention is particularly useful when using the DMT and PAG
processes for polymer array synthesis.
[0039] When synthesizing nucleic acid arrays, the photochemical
processes used to fabricate the arrays is preferably activated with
light having a wavelength greater than 365 nm to avoid
photochemical degradation of the polynucleotides used to create the
polymer arrays. Other wavelengths may be desirable for other
probes. Many photoacid generators (PAGs) based on o-nitrobenzyl
chemistry are useful at 365 nm. Further, when using the mirror
array from Texas Instruments discussed above, the PAG is preferably
sensitive above 400 nm to avoid damage to the mirror array. To
achieve this, p-nitrobenzyl esters can be used in conjunction with
a photosensitizer. For example, p-nitrobenzyltosylate and
2-ethyl-9,10-dimethoxy-anthracene can be used to photochemically
generate toluenesulfonic acid at 405 nm. See S. C. Busman and J. E.
Trend, J. Imag. Technol., 1985, 11, 191; A. Nishida, T. Hamada, and
O. Yonemitsu, J. Org. Chem., 1988, 53, 3386. In this system, the
sensitizer absorbs the light and then transfers the energy to the
p-nitrobenzyltosylate, causing dissociation and the subsequent
release of toluensulfonic acid. Alternate sensitizers, such as
pyrene, N,N-dimethylnapthylamine, perylene, phenothiazine,
canthone, thiocanthone, actophenone, and benzophenone that absorb
light at other wavelengths are also useful.
[0040] A variety of photoresists sensitive to 436-nm light are
available for use in polymer array synthesis and will avoid
photochemical degradation of the polynucleotides.
[0041] A second preferred mechanical modulator that may be used in
the invention is the Grating Light Valve.TM. (GLV.TM.) available
from Silicon LightMachines, Sunnyvale, Calif., USA. The GLV.TM.
relies on micromachined pixels that can be programmed to be either
reflective or diffractive (Grating Light Valve.TM. technology).
Information regarding certain of the mechanical modulators
discussed herein is obtained at http://www.ti.com (Texas
instruments) and http://siliconlight.com. (Silicon
LightMachines).
[0042] Although preferred spatial light modulators include the
mechanical modulators DMD.TM. available from Texas Instruments and
the GLV.TM. available from Silicon LightMachines, various types of
spatial light modulators exist and may be used in the practice of
the present invention. See Electronic Engineers' Handbook, 3.sup.rd
Ed., Fink, D. G. and Christiansen, D. Eds., McGraw-Hill Book Co.,
New York (1989). Deformable membrane mirror arrays are available
from Optron Systems Inc. (Bedford, Mass.). Liquid-crystal spatial
light modulators are available from Hamamatsu (Bridgewater, N.J.),
Spatialight (Novato, Calif.), and other companies. However, one
skilled in the art must be careful to select the proper light
source and processing chemistries to ensure that the liquid-crystal
spatial light modulator is not damaged since these devices may be
susceptible to damage by various ultraviolet (UV) light.
Liquid-crystal displays (LCD; e.g., in calculators and notebook
computers) are also spatial light modulators useful for
photolithography particularly to synthesize large features.
However, reduction optics would be required to synthesize smaller
features using LCDs.
[0043] Some spatial light modulators may be better suited than the
Texas Instruments device for use with UV light and would therefore
be compatible with a wider range of photoresist chemistries. One
skilled in the art will choose the spatial modulator that is
compatible with the chosen wavelength of illumination and synthesis
chemistries employed. For example, the device from Texas
Instruments DMD.TM. should not be used with UV illumination because
its micro-mirror array may be damaged by UV light. However, if the
passivation layer of the micro-mirror array is modified or removed,
the Texas Instruments DMD.TM. could be used in the invention with
UV light.
[0044] One embodiment that is particularly useful when extremely
high resolution is require involves imaging the micro-mirror array
using a system of the type shown in FIG. 2. In this system, a lens
12 images the micro-mirror array 11 (e.g., DMD.TM. or GLV.TM.) onto
an array 10 having an array of micro-lenses 15 or non-imaging light
concentrators. Each element of the array 10 focuses light onto the
chip or wafer, e.g., Gene Chip array 14. Each micro-lens 15
produces an image of one pixel of the micro-mirror array 11. Optics
16, including a shaping lens 17 may be included to translate light
from a light source 13 onto the micro-mirror array 11.
[0045] For example, if an SVGA DLP.TM. device is imaged with 1:1
magnification onto a micro-lens array 10, an appropriate micro-lens
array 10 can consist of 800.times.600 lenses (micro-lenses 15) with
17 .mu.m center-to-center spacing. Alternatively, the micro-lens
array can consist of 400.times.300 17 .mu.m diameter lenses with 34
.mu.m center-to-center spacing, and with opaque material (e.g.,
chrome) between micro-lenses 15. One advantage of this alternative
is that cross-talk between pixels is reduced. The light incident
upon each micro-lens 15 can be focused to a spot size of 1-2 .mu.m.
Because the spot size is much less than the spacing between
micro-lenses, a 2-axis translation stage (having, in these
examples, a range of travel of at least either 17 .mu.m.times.17
.mu.m or 34 .mu.m.times.34 .mu.m) is necessary if complete coverage
of the chip or wafer 14 is desired.
[0046] Micro-lenses 15 can be diffractive, refractive, or hybrid
(diffractive and refractive). Refractive micro-lenses can be
conventional or gradient-index. A portion of a diffractive
micro-lens array 10 is shown in FIG. 3 and has individual
micro-lenses formed as circles commonly known as Fresnel Zone
Plates 20. Alternatively an array of non-imaging light
concentrators can be employed. An example of such an approach would
include a short piece of optical fiber which may be tapered to a
small tip.
[0047] Furthermore, some spatial light modulators are designed to
modulate transmitted rather than reflected light. An example of a
transmissive spatial light modulator is a liquid crystal display
(LCD) and is illustrated in another embodiment, shown in FIG. 4.
This embodiment includes a light source 33 providing light 35,
transmissive spatial light modulator 31 and a computer 39 providing
electronic control signals to the transmissive spatial light
modulator 31 through cables 40 so as to transmit a desired light
image 38 on the chip or wafer 34; The computer 39 may be, for
example, a unique programmable controller, a personal computer
(PC), or a CAD system used to design the desired image pattern.
[0048] Using a transmissive spatial light modulator has even
additional advantages over the conventional optical lithography
system. Reflective spatial light modulators require a large working
distance between the modulator and the lens so that the lens does
not block the incident light. Designing a high performance lens
with a large working distance is more difficult than designing a
lens of equivalent performance with no constraints on the working
distance. With a transmissive spatial light modulator the working
distance does not have to be long and lens design is therefore
easier. In fact, as show in FIG. 4, some transmissive spatial light
modulators 31 might be useful for proximity or contact printing
with no lens at all, by locating the modulator very close to the
chip or wafer 34.
[0049] In fact, the transmissive spatial light modulator in the
embodiment of FIG. 4 could be replaced by an LED array or a
semiconductor laser arrays emitting light of the appropriate
wavelength, each of which not only may be operated to dynamically
define a desired image but also act as the light source. Thus, as
modified, this embodiment would be simplified so as to not require
a separate light source.
[0050] Although discussed herein in reference to polymer array
synthesis, one skilled in the art will appreciate that the present
invention has a variety of applications including, among others,
silicon micromachining and custom semiconductor chip manufacturing.
However, use of some types of spatial light modulators with the
invention may result in limiting the types of geometries available
in silicon micromachining and custom semiconductor chip
manufacturing applications. It is understood that the examples and
embodiments described herein are for illustrative purposes only and
that various modifications or changes in light thereof will be
suggested to persons skilled in the art and are to be included
within the spirit and purview of this application and scope of the
appended claims.
[0051] All publications, patents, and patent applications cited
herein are hereby incorporated by reference in their entirety for
all purposes application Ser. No. 08/426,202 (filed Apr. 21, 1995)
relates to the present invention and is hereby incorporated by
reference for all purposes.
* * * * *
References