U.S. patent application number 10/632255 was filed with the patent office on 2004-06-17 for affinity based self-assembly systems and devices for photonic and electronic applications.
This patent application is currently assigned to Nanotronics, Inc.. Invention is credited to Heller, Michael J..
Application Number | 20040115696 10/632255 |
Document ID | / |
Family ID | 25060614 |
Filed Date | 2004-06-17 |
United States Patent
Application |
20040115696 |
Kind Code |
A1 |
Heller, Michael J. |
June 17, 2004 |
Affinity based self-assembly systems and devices for photonic and
electronic applications
Abstract
This invention relates to methodologies and techniques that
utilize programmable functionalized self-assembling nucleic acids,
nucleic acid modified structures, and other selective affinity or
binding moieties as building blocks for creating molecular
electronic and photonic mechanisms; organizing, assembling, and
interconnecting nanostructures, submicron- and micron-sized
components onto silicon or other materials; organizing, assembling,
and interconnecting nanostructures, submicron- and micron-sized
components within perimeters of microelectronic or optoelectronic
components/devices; and creating and manufacturing photonic and
electronic structures, devices, and systems. In one aspect of this
invention, a method for forming a multiple identity substrate
material is provided comprising the steps of: providing a first
affinity sequence at multiple locations on a support, providing a
functionalized second affinity sequence, which reacts with the
first affinity sequence, and has an unhybridized overhang sequence,
and selectively cross-linking first affinity sequences and second
affinity sequences.
Inventors: |
Heller, Michael J.;
(Encinitas, CA) |
Correspondence
Address: |
O'MELVENY & MEYERS
114 PACIFICA, SUITE 100
IRVINE
CA
92618
US
|
Assignee: |
Nanotronics, Inc.
San Diego
CA
|
Family ID: |
25060614 |
Appl. No.: |
10/632255 |
Filed: |
July 31, 2003 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10632255 |
Jul 31, 2003 |
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08760933 |
Dec 6, 1996 |
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6652808 |
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Current U.S.
Class: |
435/6.12 ;
257/E21.705; 427/2.11; 435/287.2 |
Current CPC
Class: |
H01L 2924/01006
20130101; H01L 2924/01052 20130101; G11B 7/0045 20130101; B01J
2219/00317 20130101; B01J 2219/00605 20130101; B01J 2219/00725
20130101; B01L 3/502761 20130101; H01L 2924/10253 20130101; B01L
2200/025 20130101; H01L 2924/01013 20130101; H01L 2924/01047
20130101; B01J 2219/00497 20130101; H01L 2924/01023 20130101; B01J
2219/00626 20130101; C12Q 1/6837 20130101; B01J 19/0046 20130101;
B82B 3/00 20130101; C12Q 1/6816 20130101; G11C 13/04 20130101; H01L
21/7806 20130101; B01L 2300/0636 20130101; B01J 2219/00608
20130101; B01J 2219/00659 20130101; B01J 2219/00689 20130101; C07K
1/045 20130101; C40B 50/14 20130101; H01L 51/0595 20130101; G11B
7/00455 20130101; B01L 2300/0645 20130101; G11C 13/0019 20130101;
C40B 40/06 20130101; H01L 51/0093 20130101; H01L 2924/14 20130101;
B01J 2219/00617 20130101; H01L 2924/01082 20130101; H01L 2924/12042
20130101; B01J 2219/00527 20130101; B01L 3/502715 20130101; H01L
2224/95085 20130101; H01L 2924/01039 20130101; B82Y 5/00 20130101;
C12Q 1/6813 20130101; B01J 2219/00545 20130101; B82Y 30/00
20130101; B82Y 40/00 20130101; H01L 2924/01011 20130101; H01L
2924/01019 20130101; H01L 2924/10329 20130101; B01L 2400/0421
20130101; C40B 40/08 20130101; G06N 3/002 20130101; C12Q 1/6818
20130101; G11B 7/005 20130101; G11B 7/244 20130101; B01J 2219/00707
20130101; H01L 2924/0102 20130101; C40B 40/12 20130101; C12Q 1/6825
20130101; B01J 2219/00637 20130101; B82Y 10/00 20130101; B82Y 20/00
20130101; H01L 25/50 20130101; H01L 2924/01049 20130101; B01J
2219/00529 20130101; B01J 2219/00536 20130101; B01J 2219/0072
20130101; G06N 3/123 20130101; H01L 2924/10336 20130101; B01J
2219/00731 20130101; H01L 2924/01075 20130101; H01L 2924/01079
20130101; B01J 2219/00596 20130101; B01J 2219/00711 20130101; B01J
2219/00722 20130101; C07K 1/047 20130101; C40B 70/00 20130101; H01L
2224/95147 20130101; B01J 2219/00315 20130101; B01L 3/502707
20130101; B01L 3/5085 20130101; C40B 40/10 20130101; G11B 7/0052
20130101; H01L 2924/01072 20130101; B01J 2219/00653 20130101; C07H
21/00 20130101; H01L 2924/12041 20130101; G11C 13/0014 20130101;
H01L 2924/01322 20130101; H01L 2224/95145 20130101; H01L 2924/01025
20130101; H01L 2924/01033 20130101; B01L 2200/0663 20130101; C07K
1/04 20130101; C40B 60/14 20130101; H01L 25/16 20130101; B01J
2219/00686 20130101; H01L 24/95 20130101; B01J 2219/00713 20130101;
C07B 2200/11 20130101; G11B 7/24 20130101; H01L 2924/01005
20130101; B01J 2219/00585 20130101; B01L 2200/12 20130101; G02B
6/1225 20130101; G11B 7/0037 20130101; B01J 19/0093 20130101; G01N
33/54366 20130101; G06N 3/061 20130101; B01J 2219/0059 20130101;
B01J 2219/00612 20130101; C12Q 1/6837 20130101; C12Q 2565/515
20130101; C12Q 2565/607 20130101; H01L 2924/10253 20130101; H01L
2924/00 20130101; H01L 2924/12042 20130101; H01L 2924/00
20130101 |
Class at
Publication: |
435/006 ;
427/002.11; 435/287.2 |
International
Class: |
C12Q 001/68; G01N
015/06; G01N 033/00; G01N 033/48; C12M 001/34 |
Goverment Interests
[0002] The Federal Government may have rights in certain claims of
this patent under Contract No. F 30602-94-C-0179 with the United
States Air Force.
Claims
We claim:
1. A method for forming a multiple identity substrate material
comprising the steps of: providing a first affinity sequence at
multiple locations on a support; providing a functionalized second
affinity sequence, which reacts with the first affinity sequence,
and has an unhybridized overhang sequence; and selectively
cross-linking first affinity sequences and second affinity
sequences.
2. The method of claim 1, wherein the cross-linking is performed by
UV irradiation of psoralen.
3. The method of claim 1, wherein at least one location on the
support with the first affinity sequence is masked to prevent
cross-linking of the first and second affinity sequences.
4. The method of claim 1, wherein the first affinity sequence is
covalently attached to the support.
5. The method of claim 4, wherein the support is reacted with
aminopropyltriethoxysilane (APS) reagent before the first affinity
sequence is attached.
6. The method of claim 4, wherein the first affinity sequence is
reacted to form a dialdehyde group at a terminal position of the
first affinity sequence.
7. The method of claim 1, further comprising the steps of:
dehybridizing the second affinity sequences that are not
cross-linked; providing a functionalized third affinity sequence,
which reacts with the second affinity sequence, and has an
unhybridized overhang sequence; and selectively cross-linking the
second and third affinity sequences.
8. The method of claim 8, wherein the cross-linking is performed by
UV irradiation with psoralen.
9. The method of claim 7, wherein at least one location on the
support is masked to prevent cross-linking of the second and third
affinity sequences.
10. The method of claim 1, further comprising providing a fourth
affinity sequence that hybridizes with the first affinity sequence
and includes a fluorescent label.
11. The method of claim 1, further comprising providing a fifth
affinity sequence that hybridizes with the second affinity sequence
and includes a fluorescent label.
12. The method of claim 7, further comprising a sixth affinity
sequence that hybridizes with the third affinity sequence and
includes a fluorescent label
Description
RELATED APPLICATION INFORMATION
[0001] This application is a continuation of application Ser. No.
08/760,933, filed Dec. 6, 1996, now allowed, which is expressly
incorporated herein by reference in its entirety.
FIELD OF THE INVENTION
[0003] This invention relates to methodologies and techniques which
utilize programmable functionalized self-assembling nucleic acids,
nucleic acid modified structures, and other selective affinity or
binding moieties as building blocks for: (1) creating molecular
electronic and photonic mechanisms; (2) for the organization,
assembly, and interconnection of nanostructures, submicron and
micron sized components onto silicon or other materials; (3) for
the organization, assembly, and interconnection of nanostructures,
submicron and micron sized components within perimeters of
microelectronic or optoelectronic components and devices; (4) for
creating, arraying, and manufacturing photonic and electronic
structures, devices, and systems; (5) for the development of a high
bit density (large byte) three and four dimensional optical data
storage materials and devices; and (6) for development of low
density optical memory for applications in authentication,
anti-counterfeiting, and encryption of information in document or
goods. This invention also relates to associated microelectronic
and optoelectronic devices, systems, and manufacturing platforms
which provide electric field transport and selective addressing of
self-assembling, nanostructures, sub-micron and micron sized
components to selected locations on the device itself or onto other
substrate materials.
BACKGROUND OF THE INVENTION
[0004] The fields of molecular electronics/photonics and
nanotechnology offer immense technological promise for the future.
Nanotechnology is defined as a projected technology based on a
generalized ability to build objects to complex atomic
specifications. Drexler, Proc. Natl. Acad. Sci USA, 78:5275-5278,
(1981). Nanotechnology generally means an atom-by-atom or
molecule-by-molecule control for organizing and building complex
structures all the way to the macroscopic level. Nanotechnology is
a bottom-up approach, in contrast to a top-down strategy like
present lithographic techniques used in the semiconductor and
integrated circuit industries. The success of nanotechnology may be
based on the development of programmable self-assembling molecular
units and molecular level machine tools, so-called assemblers,
which will enable the construction of a wide range of molecular
structures and devices. Drexler, "Engines of Creation," Doubleday
Publishing Co., New York, N.Y. (1986).
[0005] Present molecular electronic/photonic technology includes
numerous efforts from diverse fields of scientists and engineers.
Carter, ed., "Molecular Electronic Devices II," Marcel Dekker, Inc,
New York, N.Y. (1987). Those fields include organic polymer based
rectifiers, Metzger et al., "Molecular Electronic Devices II,"
Carter, ed., Marcel Dekker, New York, N.Y., pp.5-25 (1987),
conducting conjugated polymers, MacDiarmid et al., Synthetic
Metals, 18:285 (1987), electronic properties of organic thin films
or Langmuir-Blogett films, Watanabe et al., Synthetic Metals,
28:C473 (1989), molecular shift registers based on electron
transfer, Hopfield et al., Science, 241:817 (1988), and a
self-assembly system based on synthetically modified lipids which
form a variety of different "tubular" microstructures. Singh et
al., "Applied Bioactive Polymeric Materials," Plenum Press, New
York, N.Y., pp. 239-249 (1988). Molecular optical or photonic
devices based on conjugated organic polymers, Baker et al.,
Synthetic Metals, 28:D639 (1989), and nonlinear organic materials
have also been described. Potember et al., Proc. Annual Conf. IEEE
in Medicine and Biology, Part 4/6:1302-1303 (1989).
[0006] However, none of the cited references describe a
sophisticated or programmable level of self-organization or
self-assembly. Typically the actual molecular component which
carries out the electronic and/or photonic mechanism is a natural
biological protein or other molecule. Akaike et al., Proc. Annual
Conf. IEEE in Medicine and Biology, Part 4/6:1337-1338 (1989).
There are presently no examples of a totally synthetic programmable
self-assembling molecule which produces an efficient electronic or
photonic structure, mechanism or device.
[0007] Progress in understanding self-assembly in biological
systems is relevant to nanotechnology. Drexler, Proc. Natl. Acad.
Sci USA, 78:5275-5278 (1981), and Drexler, "Engines of Creation,"
Doubleday Publishing Co., New York, N.Y. (1986). Areas of
significant progress include the organization of the light
harvesting photosynthetic systems, the energy transducing electron
transport systems, the visual process, nerve conduction and the
structure and function of the protein components which make up
these systems. The so called bio-chips described the use of
synthetically or biologically modified proteins to construct
molecular electronic devices. Haddon et al., Proc. Natl. Acad. Sci.
USA, 82:1874-1878 (1985), McAlear et al., "Molecular Electronic
Devices II," Carter ed., Marcel Dekker, Inc., New York N.Y.,
pp.623-633 (1987).
[0008] Some work on synthetic proteins (polypeptides) has been
carried out with the objective of developing conducting networks.
McAlear et al., "Molecular Electronic Devices," Carter ed., Marcel
Dekker, New York, N.Y., pp.175-180 (1982). Other workers have
speculated that nucleic acid based bio-chips may be more promising.
Robinson et al., "The Design of a Biochip: a Self-Assembling
Molecular-Scale Memory Device," Protein Engineering, 1:295-300
(1987).
[0009] Great strides have also been made in the understanding of
the structure and function of the nucleic acids, deoxyribonucleic
acid or DNA, Watson, et al., in "Molecular Biology of the Gene,"
Vol. 1, Benjamin Publishing Co., Menlo Park, Calif. (1987), which
is the carrier of genetic information in all living organisms (See
FIG. 1). In DNA, information is encoded in the linear sequence of
nucleotides by their base units adenine, guanine, cytosine, and
thymidine (A, G, C, and T). Single strands of DNA (or
polynucleotide) have the unique property of recognizing and
binding, by hybridization, to their complementary sequence to form
a double stranded nucleic acid duplex structure. This is possible
because of the inherent base-pairing properties of the nucleic
acids: A recognizes T, and G recognizes C. This property leads to a
very high degree of specificity since any given polynucleotide
sequence will hybridize only to its exact complementary
sequence.
[0010] In addition to the molecular biology of nucleic acids, great
progress has also been made in the area of the chemical synthesis
of nucleic acids. This technology has developed so automated
instruments can now efficiently synthesize sequences over 100
nucleotides in length, at synthesis rates of 15 nucleotides per
hour. Also, many techniques have been developed for the
modification of nucleic acids with functional groups, including:
fluorophores, chromophores, affinity labels, metal chelates,
chemically reactive groups and enzymes. Smith et al., Nature,
321:674-679 (1986); Agarawal et al., Nucleic Acids Research,
14:6227-6245 (1986); Chu et al., Nucleic Acids Research,
16:3671-3691 (1988).
[0011] An impetus for developing both the synthesis and
modification of nucleic acids has been the potential for their use
in clinical diagnostic assays, an area also referred to as DNA
probe diagnostics. Simple photonic mechanisms have been
incorporated into modified oligonucleotides in an effort to impart
sensitive fluorescent detection properties into the DNA probe
diagnostic assay systems. This approach involved fluorophore and
chemilluminescent-labeled oligonucleotides which carry out Forster
nonradiative energy transfer. Heller et al., "Rapid Detection and
Identification of Infectious Agents," Kingsbury et al., eds.,
Academic Press, New York, N.Y. pp. 345-356 (1985). Forster
nonradiative energy transfer is a process by which a fluorescent
donor group excited at one wavelength transfers its absorbed energy
by a resonant dipole coupling process to a suitable fluorescent
acceptor group. The efficiency of energy transfer between a
suitable donor and acceptor group has a 1/r.sup.6 distance
dependency (see Lakowicz et al., "Principles of Fluorescent
Spectroscopy," Plenum Press, New York, N.Y., Chap. 10, pp. 305-337
(1983)).
[0012] As to photonic devices, they can generally be fabricated in
dense arrays using well developed micro-fabrication techniques.
However, they can only be integrated over small areas limited by
the relatively high defect densities of the substrates employed. In
order to be useful and economically viable, these devices must in
many cases, be used within large area silicon integrated circuits.
A good example of this issue is the vertical cavity surface
emitting lasers. To address many potential applications, it would
be highly desirable to integrate these devices with large area
silicon IC's. A major obstacle in the integration of these new
devices with silicon is the existence of material and geometrical
incompatibilities. These devices need to be integrated on silicon
in large sparse arrays with minimal performance degradation, and
without affecting the underlying silicon circuits. Over the past
years, a number of component assembly technologies have been
extensively investigated regarding the integration of such compound
semiconductor devices on silicon. These include hybrid flip-chip
bonding or epitaxial lift-off and other direct bonding methods.
Although these hybrid technologies have made significant progress
and several component demonstrations have shown the viability of
these techniques, these methods do not address the problem of
geometrical incompatibility. That is, the dimensions with which the
specialty devices are fabricated on their mother substrate must be
conserved when they are coupled onto the host substrate. This makes
the integration of small area devices on large area components
economically unfeasible.
[0013] A major obstacle in the integration of these new devices
with silicon is the existence of material and geometrical
incompatibilities. These devices need to be integrated on silicon
in large sparse arrays with minimal performance degradation, and
without affecting the underlying silicon circuits. Over the past
years, a number of component assembly technologies have been
extensively investigated regarding the integration of such compound
semiconductor devices on silicon. These include hybrid flip-chip
bonding or epitaxial lift-off and other direct bonding methods.
Although these hybrid technologies have made significant progress
and several component demonstrations have shown the viability of
these techniques, these methods do not address the problem of
geometrical incompatibility. That is, the dimensions with which the
specialty devices are fabricated on their mother substrate must be
conserved when they are coupled or grafted onto the silicon
board.
[0014] The prior art has no integration technique that is capable
of creating a sparse array of devices distributed over a large
area, when the devices are originally fabricated densely over small
areas. This makes large area components made up from integration of
micron size devices economically unfeasible. To solve this problem,
the electronics industry employs a hierarchy of packaging
techniques. However, this problem remains unsolved when a regular
array of devices is needed on large areas with a relatively small
pitch. This problem is probably most noticeable through the high
cost associated with the implementation of matrix addressed
displays, where the silicon active matrix consists of small
transistors that need to be distributed over a large area. Thus,
prior art microfabrication techniques limit devices to small area
components where a dense array of devices are integrated. However,
there are a number of important applications that could benefit
from specialty devices being integrated more sparsely over large
areas.
[0015] One possible method for removing the geometrical limitations
is the further development of semiconductor substrate materials to
the point where their defect densities approaches that of silicon.
This is a long and expensive process that requires incremental
progress. A second approach is the development of special robots
capable of handling micron and sub-micron size devices and able to
graft them to appropriate places. This also seems impractical
because the grafting process will remain sequential where one
device may be grafted after another, requiring impractical
processing times. In any case, both of these approaches may be
limited to motherboard dimensions on the order of 10 cm.
[0016] With regard to memories, data processing engines have been
physically and conceptually separated from the memory which stores
the data and program commands. As processor speed has increased
over time, there has been a continuous press for larger memories
and faster access. Recent advances in processor speed have caused
system bottlenecks in access to memory. This restriction is
critical because delays in obtaining instructions or data may cause
significant processor wait time, resulting in loss of valuable
processing time.
[0017] Various approaches have been taken to solve these concerns.
Generally, the solutions include using various types of memory
which have different attributes. For example, it is common to use a
relatively small amount of fast, and typically expensive, memory
directly associated with the processor units, typically called
cache memory. Additionally, larger capacity, but generally slower,
memory such as DRAM or SRAM is associated with the CPU. This
intermediate memory is often large enough for a small number of
current applications, but not large enough to hold all system
programs and data. Mass storage memory, which is ordinary very
large, but relatively inexpensive, is relatively slow. While
advances have been continually made in improving the size and speed
of all types of memory, and generally reducing the cost per bit of
memory, there remains a substantial need especially to serve yet
faster processors.
[0018] For the last 20 years most mass storage devices have
utilized a rotating memory medium. Magnetic media have been used
for both "floppy" (flexible) disks or "hard" disk drives.
Information is stored by the presence or absence of magnetization
at defined physical locations on the disk. Ordinarily, magnetic
media are "read-write" memories in that the memory may be both
written to and read from by the system. Data is written to or read
from the disk by heads placed close to the surface of the disk.
[0019] A more recent development in rotating mass storage media are
the optical media. Compact disks are read only memory in which the
presence or absence of physical deformations in the disk indicates
the data. The information is read by use of a focused laser beam,
in which the change in reflectance properties from the disk
indicate the data states. Also in the optical realm are various
optical memories which utilize magnetooptic properties in the
writing and reading of data. These disks are both read only, write
once read many ("WORM") drives and multiple read-write memories.
Generally, optical media have proved to have a larger storage
capacity, but higher costs per bit and limited write ability, as
compared with magnetic media.
[0020] Several proposals have been made for using polymers for
electronic based molecular memories. For example, Hopfield, J. J.,
Onuchic, J. N. and Beratan, D. N., "A Molecular Shift Register",
Science, 241, p. 817, 1988, discloses a polymer based shift
register memory which incorporates charge transfer groups. Other
workers have proposed an electronic based DNA memory (see Robinson
et al, "The Design of a Biochip: A Self-Assembling Molecular-Scale
Memory Device", Protein Engineering, 1:295-300 (1987)). In this
case, DNA is used with electron conducting polymers for a molecular
memory device. Both concepts for these molecular electronic
memories do not provide a viable mechanism for inputting data
(write) and for outputting data (read).
[0021] Molecular electronic memories have been particularly
disappointing in their practical results. While proposals have been
made, and minimal existence proofs performed, generally these
systems have not been converted to commercial reality. Further, a
specific deficiency of the system described above is that a
sequential memory is typically substantially slower than a random
access memory for use in most systems.
[0022] The optical memories described above suffer from the
particular problem of requiring use of optical systems which are
diffraction limited. This imposes size restrictions upon the
minimum size of a data bit, thereby limiting memory density. This
is an inherent limit in systems which store a single bit of data at
a given physical memory location. Further, in all optical memory
systems described above, the information is stored on a bit-by-bit
basis, such that only a single bit of data is obtained by accessing
a giving physical location in memory. While word-wide memory access
systems do exist, generally they store but a single bit of
information at a given location, thereby requiring substantially
the same amount of physical memory space whether accessed in a bit
manner or word-wide manner.
[0023] While systems have generally increased in speed and storage
density, and decreased in cost per bit, there remains a clear gap
at present between processor speed and system requirements. See
generally, "New Memory Architectures to Boost Performance", Tom R.
Halfhill, Byte, July, 1993, pp 86 and 87. Despite the general
desirability of memories which are faster, denser and cheaper per
bit, and the specific critical need for mass memory which can meet
the demands of modern day processor systems speed, no completely
satisfactory solution has been advanced heretofore. The fundamental
limitations on the currently existing paradigms cannot be overcome
by evolutionary enhancements in those systems.
[0024] Despite the clear desirability for new and improved
apparatus and methods in this field, no optimal solution has been
proposed previously.
SUMMARY OF THE INVENTION
[0025] Increasingly, the technologies of communication, information
processing, and data storage are beginning to depend upon
highly-integrated arrays of small, fast electronic and photonic
devices. As device sizes scale down and array sizes increase,
conventional integration techniques become increasingly costly. The
dimensions of photonic and electronic devices permit the use of
molecular biological engineering for the integration and
manufacturing of photonic and electronic array components. This
invention relates to methodologies and manufacturing techniques
which utilize programmable functionalized self-assembling nucleic
acids, nucleic acid modified structures, and other selective
affinity or binding moieties as building blocks for: (1) creating
molecular electronic and photonic mechanisms; (2) for the
organization, assembly, and interconnection of nanostructures,
submicron and micron sized components onto silicon or other
materials; (3) for the organization, assembly, and interconnection
of nanostructures, submicron and micron sized components within
perimeters of microelectronic or optoelectronic components and
devices; (4) for creating, arraying, and manufacturing photonic and
electronic structures, devices, and systems; (5) for the
development of a high bit density (large byte) three and four
dimensional optical data storage materials and devices; and (6) for
development of low density optical memory for applications in
authentication, anti-counterfeiting, and encryption of information
in documents or goods. This invention also relates to associated
microelectronic and optoelectronic devices, systems, and
manufacturing platforms which provide electric field transport and
selective addressing of self-assembling, nanostructures, sub-micron
and micron size components to selected locations on the device
itself or onto other substrate materials.
[0026] Functionalized nucleic acids based polymers (e.g., DNA, RNA,
peptide nucleic acids, methyphosphonates) constitute a vehicle to
assemble large numbers of photonic and electronic devices and
systems, utilizing the base-pair coding property of the DNA which
allows specific complementary double stranded DNA structures to be
formed. This unique property of DNA provides a programmable
recognition code (via the DNA sequence) which can be used for
specific placement and alignment of nanostructures.
[0027] In the preferred embodiment, the process by which photonic
devices would be aligned, involves first coating them with a
specific DNA sequence. The area of the host substrate where
attachment of the devices is desired are coated with the specific
complementary DNA sequence. The substrate and DNA-covered devices
are released into a solution and hybridization between
complementary DNA strands occurs. Hybridization effectively grafts
the devices to their proper receptor locations on the
substrate.
[0028] More broadly, the invention in this respect relates to a
method for the fabrication of micro scale and nanoscale devices
comprising the steps of: fabricating first component devices on a
first support, releasing at least one first component device from
the first support, transporting the first component device to a
second support, and attaching the first component device to the
second support.
[0029] Some potential applications for these techniques are: (1)
fabricating light emitter arrays over large surfaces; (2) assembly
of two or three-dimensional photonic crystal structures; and (3)
manufacturing of various hybrid-integrated components including
flat panel displays, medical diagnostic equipment and data storage
systems.
[0030] As photonics plays an increasingly important role in
information processing, communication and storage systems it will
deliver faster, smaller, more power efficient, and functionally
versatile integrated systems at lower cost. New fabrication
technologies including nanostructure fabrication, integration and
self-assembly techniques are used. As device dimensions shrink to
submicron levels, it becomes important to utilize the inventive
concepts employing molecular biological engineering concepts and
principles as manufacturing techniques for the fabrication of
integrated photonic and electronic devices.
[0031] These inventions relate to nanostructures, submicron and
micron-sized structures incorporating synthetic DNA polymers. This
includes DNA modified with small chromophore molecules, to large
structures (e.g., micron-sized) which are modified with DNA
sequences. Synthetic DNA polymers can be designed with highly
specific binding affinities. When covalently attached to nanoscale
organic and metallic structures or micron scale semiconductor
component devices, DNA polymers can provide a self-assembly
fabrication mechanism. This mechanism can be used for both the
selective grafting of the devices to specific pre-programmed
locations on a desired surface, and for the clustering of devices
into pre-programmed 2-D or 3-D lattices. For grafting of photonic
or electronic component devices onto host substrates, DNA polymers
with complementary sequences are first synthesized. The photonic
component devices and desired areas of the host substrate (receptor
areas) are coated with the complementary DNA sequences. The host
substrates are then introduced into a solution.
[0032] In one aspect of this invention, a method for fabrication of
nanoscale and microscale structures is provided comprising the
steps of: providing a structure with multiple affinity surface
identities, orienting the structure in an electric field, and
reacting the oriented structure with an affinity site.
[0033] In yet another aspect of this invention, a method for
forming a multiple identity substrate material is provided
comprising the steps of: providing a first affinity sequence at
multiple locations on a support, providing a functionalized second
affinity sequence, which reacts with the first affinity sequence,
and has an unhybridized overhang sequence, and selectively
cross-linking first affinity sequences and second affinity
sequences.
[0034] In yet another aspect of this invention, a method for the
assembly of chromophoric structures is provided comprising the
steps of: selectively irradiating a photoactivatable region,
whereby an electric field is generated corresponding to the region,
providing charged reactants in solution which includes the electric
field, and repeating the selective irradiation to sequentially
assemble the chromophoric structures.
[0035] It is an object of this invention to enable nanotechnology
and self-assembly technology by the development of programmable
self-assembling molecular construction units.
BRIEF DESCRIPTION OF THE DRAWINGS
[0036] FIGS. 1A and 1B show DNA structure and its related physical
dimensions.
[0037] FIG. 2 is a flow diagram of self-assembly processes.
[0038] FIG. 3A is a perspective drawing of the apparatus and method
for redistribution of photonic devices fabricated as dense arrays
onto the host substrate without mother substrate layout
constraints.
[0039] FIG. 3B is a perspective view of a clustering of nanospheres
by DNA assisted self-assembly to form synthetic photonic
crystals.
[0040] FIG. 4 shows a cross-section of an attachment mechanism for
attaching DNA to silicon.
[0041] FIG. 5 shows steps for preparation of photonic devices for
self assembly.
[0042] FIG. 6 shows a plan view of a structure for selective
attachment of fluorescent DNA sequences to aluminum pads on silicon
VLSI chips.
[0043] FIG. 7 is a plan view of a UV write/imaging into monolayers
of DNA on silicon/silicon dioxide/aluminum.
[0044] FIG. 8A is a plan view of a UV image mask write followed by
hybridization into DNA optical storage material.
[0045] FIG. 8B is a plan view of a UV image mask write into DNA
optical storage material (10 micron resolution).
[0046] FIG. 9 is a cross-sectional view of an apparatus and method
for preparing multiple write materials.
[0047] FIG. 10 is a cross-sectional view of a step in the process
for preparing DNA write materials wherein a DNA sequence B is
hybridized to sequence A bound to the substrate leaving an
unhybridized overhang sequence for subsequent hybridization.
[0048] FIG. 11 is a cross-sectional view of a step in the process
for preparing DNA write materials wherein location number 1 is
masked from ultraviolet exposure while unmasked locations are
exposed permitting cross-linking between sequences A and B.
[0049] FIG. 12 is a cross-sectional view of a step in the process
for preparing DNA write materials wherein dehybridization is
carried out to remove the non-crosslinked sequence B from the
previously masked location.
[0050] FIG. 13 is a cross-sectional view of a step in the process
for preparing DNA write materials wherein a functionalized DNA
sequence C is hybridized to sequence B, and the process
repeated.
[0051] FIG. 14 is a cross-sectional view of a step in the process
for preparing DNA write materials wherein locations 1 and 2 are
masked while locations 3 and 4 are exposed resulting in
cross-linking of sequences B and C.
[0052] FIG. 15 is a cross-sectional view of a step in the process
for preparing DNA write materials wherein dehybridization is
carried out to remove sequence C from location 2, an permanent DNA
sequence B being present at location 2.
[0053] FIG. 16 is a cross-sectional view of a step in the process
for preparing DNA write materials wherein a functionalized DNA
sequence D is hybridized to sequence C.
[0054] FIG. 17 is a cross-sectional view of a step in the process
for preparing DNA write materials wherein locations 1, 2 and 3 are
masked while location 4 is exposed to light causing the
cross-linking of DNA sequence D to DNA sequence C.
[0055] FIG. 18 is a cross-sectional view of a step in the process
for preparing DNA write materials wherein dehybridization is
carried out to remove DNA sequence D from location 3, a permanent
sequence C being present at location 3 and a permanent sequence D
being present at location 4.
[0056] FIG. 19 is a cross-sectional view of a step in the process
for preparing DNA write materials wherein complementary DNA
sequences to A, B, C and D identities labeled with four respective
fluorescent dyes are hybridized to demonstrate each identity.
[0057] FIG. 20 is a cross-sectional view of a step in the process
for preparing DNA write materials showing the chip surface with A,
B, C and D identities.
[0058] FIG. 21 is a cross-sectional view of a step in the process
for preparing DNA write materials showing selective UV exposure
which leaves locations 1 and 3 unhybridizable and locations 2 and 4
hybridizable.
[0059] FIG. 22 is a cross-sectional view of a step in the process
for preparing DNA write materials showing the DNA complements
labeled with their respective fluorophores applied to the surface,
wherein only locations B and D hybridized their respective
fluorescent complements.
[0060] FIG. 23A is a planned image of the background fluorescence
for APS-reacted silicon substrate surface before DNA
attachment.
[0061] FIG. 23B is a planned image of the background fluorescence
level after capture DNA is bound to the APS-reacted substrate.
[0062] FIG. 24A is a planned image of a chip treated with APS and
capture DNA and then hybridized with a BODIPY Texas Red labeled
complementary probe sequence across the entire chip surface.
[0063] FIG. 24B is a planned image of the chip surface after
hybridization of a fluorescent BODIPY Texas Red labeled
complimentary probe to the non-psoralen cross-linked identity on
the right side of the chip surface.
[0064] FIG. 25A is a plan image of the chip surface after
hybridization of a fluorescent BODIPY Orange (b) complementary
probe to the (b) sequence identity on the left side of the chip
surface.
[0065] FIG. 25B is a plan image of the chip after both cross-linked
(B) and non-cross-linked (A) sides are hybridized with their
respective fluorescently labeled complimentary DNA (A) and (B)
probes.
[0066] FIG. 26A is a plan image of 160 nanometer beads (white
spherical features) electrostatically bound to a DNA polymer layer
covalently bound to a silicon dioxide derivitized surface with
partial specificity, having 10 micron square dark features where
the DNA field has been UV inactivated, the nanospheres not binding
in these areas.
[0067] FIG. 26B is a plan image of a pattern image constructed with
160 nanometer beads (white spherical features) wherein the
nanospheres are electrostatically bound to a DNA polymer layer
covalently bound to silicon dioxide derivitized surface with
partial specificity, the dark areas showing areas where the DNA
field has been UV inactivated, the nanospheres not binding in these
areas.
[0068] FIGS. 27A, B and C are cross-sectional views of apparatus
and method steps for forming fluorescently labeled sequences,
wherein FIG. 27A specifically shows a substrate with a
functionalized surface, FIG. 27B shows a substrate with a
functionalized surface further with a capture sequence A attached
to the functionalized surface, and FIG. 27C shows the substrate
with the functionalized surface, sequence A and labeled
complementary sequence hybridized.
[0069] FIGS. 28A, B, and C show cross-sectional views of apparatus
and method steps for providing multicolor images, wherein FIG. 28A
shows a portion of the surface being labeled with BODIPY Texas Red,
FIG. 28B shows a portion of the surface being labeled with BODIPY
Orange and FIG. 28C showing a portion of the surface being labeled
with BODIPY Texas Red and the other portion labeled with BODIPY
Orange.
[0070] FIG. 29 is a perspective view of a flip-chip bonding
arrangement which conserves the geometrical dimensions leading to
the coupling of small dense arrays of specialty devices onto local
regions of mother boards.
[0071] FIG. 30 shows a perspective view of global distribution of
small dense structures from small dense chips on to less dense host
boards.
[0072] FIG. 31 shows a cross-sectional view of a structure for the
self-assembly of micro or nanostructures utilizing a selective glue
in which speciality devices of the given type are provided with a
specific DNA polymer glue, the areas where these devices must
attach being covered with the complimentary DNA glue.
[0073] FIG. 32 shows a cross-sectional view of selective electric
field deposition of DNA onto the specially derivitized
microelectrode surfaces.
[0074] FIG. 33 shows a cross-sectional view of a micro or nanoscale
structure coupled to its host board substrate by selective DNA
hybridization between complimentary DNA strands.
[0075] FIG. 34 shows a cross-sectional view of nanostructures held
in place via a DNA bond (left-hand side) and nanostructure held by
a metallurgical contact after a high temperature cycle (right-hand
side).
[0076] FIG. 35 shows a cross-sectional view of an apparatus for the
orientation of speciality devices prior to hybridization by
physical masking and charge guiding.
[0077] FIG. 36 shows structures for the formation of nanodevices,
providing an octahedron using 3-D DNA nanoconstruction techniques
(top) and nanospheres arranged into lattice structure and bound to
surface to create a 3-D device (lower).
[0078] FIG. 37 shows the steps in a process for electric field
orientation of devices.
[0079] FIG. 38 shows further steps in the electric field
orientation process.
[0080] FIG. 39 shows a perspective view of nanostructure transport
and assembly on a microelectronic array device.
[0081] FIGS. 40A-H show the larger environment of FIG. 39, wherein
FIG. 40A shows negatively charged type 1 nanostructures moving
towards a positively biased microlocation, FIG. 40B shows
accumulated nanostructures on the positively biased microlocation,
FIG. 40C shows negatively charged type 2 nanostructures introduced
over the array and accumulated on the positively biased
microlocations, FIG. 40B shows both type 1 and type 2
nanostructures clustered on their respective locations, FIG. 40E
shows electronically assisted self-assembly beginning when
microlocation number 1 is biased negative and a center
microlocation is biased positive causing the negatively charged
type 1 nanostructures to move to the center location, FIG. 40F
shows type 1 nanostructures accumulated and hybridized to the
specific microlocation, FIG. 40G shows type 2 nanostructures moved
to the center location by biasing microlocation number 8 negative
and center location positive, and FIG. 40H shows type 2
nanostructures containing complementary DNA sequence hybridized to
type 1 nanostructures.
[0082] FIG. 41 shows images of an 8.times.8 array.
[0083] FIG. 42 shows an apparatus for attachment and orientation of
larger sized devices onto a substrate.
[0084] FIG. 43 shows an apparatus for fabrication of
nanostructures.
[0085] FIG. 44 shows an apparatus for nanofabrication of a
nanoscale device.
[0086] FIG. 45 shows a perspective view of a DNA optical storage
system.
[0087] FIGS. 46A-F show steps in a spacial light addressing
process.
IMPORTANT ASPECTS OF DNA STRUCTURE, PROPERTIES, AND SYNTHESIS
[0088] Synthetic DNA possesses a number of important properties
which make it a useful material for the applications of these
inventions. The most important are the molecular recognition (via
base pairing) and self-assembly (via hybridization) properties
which are inherent in all DNA molecules. Other important advantages
include the ability to easily synthesize DNA, and to readily modify
its structure with a variety of functional groups. We have
extensively investigated the photonic and electronic energy
transfer mechanisms in self-assembled arrangements of synthetic DNA
functionalized with a wide variety of donor and acceptor
chromophore groups. We have paid particular attention to the basic
problems involved in communicating or getting information in and
out of these molecular structures. This basic work is now being
applied to potential applications for high density optical storage
materials, which have been designed to absorb light energy at a
single wavelength and re-emit at predetermined multiple
wavelengths. We are also now using DNA polymers for the two and
three dimensional organization of micron and submicron sized
structures on silicon surfaces. This work is being directed at the
development of novel optoelectronic devices.
[0089] The DNA molecule is considered important to this invention
and the proposed applications because it is inherently programmable
and can self-assemble. Designing, synthesizing, and organizing
these systems requires nanometer range control which few other
synthetic polymer systems can match. Additionally, DNA molecules
are relatively stable and have a number of other attributes which
make them a preferred material for nanofabrication.
[0090] The underlying technology for DNA and other nucleic acid
type polymers comes from the enormous effort that has been invested
over the past fifteen years in synthetic nucleic acid chemistry.
Molecular biologists have refined techniques and DNA materials in
their pursuit of diagnostics, genetic sequencing, and drug
discovery. The basic chemistry for the efficient synthesis of DNA,
its modification, its labeling with ligands and chromophores, and
its covalent linkage to solid supports are now well developed
technologies. Synthetic DNA represents the preferred material into
which so many important structural, functional, and mechanistic
properties can be combined.
[0091] DNA polymers have three important advantages over any of the
present polymeric materials used for electronic and photonic
applications. First, DNA polymers provide a way to encode highly
specific binding-site identities o semiconductor or photonic
surfaces. These sites, produced at defined locations, could be of
microscopic (micron), sub-micron, or even molecular (nanometer)
dimension. Second, DNA polymers provide a way to specifically
connect any of these locations. The pre-programmed DNA polymers
self-organize automatically. Finally, DNA polymers provide the
building blocks for nanotechnology; they are self-organizing
materials for creating true molecular-level electronic and photonic
devices.
[0092] The specificity of DNA is inherent in the hydrogen bonding
properties of the base components (Adenine bonds only with Thymine,
and Guanine bonds only with Cytosine). These specific base pairing
properties of DNA allow complementary sequences of DNA to
"hybridize" together to form the double-stranded structure. It is
this inherent property which allows DNA polymers to be used to form
programmable self-assembling structures. Thus, when a photonic
device has one specific DNA polymer sequence attached to it, it
will only bind (hybridize) to a device or surface coated with the
complementary DNA polymer sequence. Since a large variety of DNA
sequences can be used, multiple devices, each attached to a
different DNA sequence can in principle be self-assembled
simultaneously. The following lists the important advantages of
using DNA polymers for self-assembling nanofabrication
applications:
[0093] 1. DNA polymers can by synthesized both rapidly and
efficiently with automated instruments. Conventional polymer
chemistries can be significantly more complex and costly to
develop.
[0094] 2. DNA polymers can be synthesized in lengths from 2 to 150
nucleotides, which is the appropriate size range (1 nm to 60 nm)
for self-assembling unit cells.
[0095] 3. DNA polymers can be synthesized with any desired base
sequence, therein providing programmable recognition for an almost
unlimited number of specific connections.
[0096] 4. DNA polymers with unique sequences of as few as ten
nucleotides are highly specific and will bind only to their
complementary sequence. Thus, the material allows specific
connections as small as 3.4 nm to be made between molecular
units.
[0097] 5. DNA polymers can be covalently labeled with fluorophores,
chromophores, affinity labels, metal chelates, chemically reactive
functional groups and enzymes. This allows important photonic and
electronic properties to be directly incorporated into the DNA
polymers.
[0098] 6. DNA polymers can be modified at any position in their
sequence, and at several places within the individual nucleotide
unit. This provides a means to position functional groups for
maximum performance.
[0099] 7. DNA polymers can be both covalently and non-covalently
linked to solid surfaces: glass, metals, silicon, organic polymers,
and bio-polymers. These attachment chemistries are both existing
and easily developed.
[0100] 8. The backbone structure of the DNA molecule itself can be
highly modified to produce different properties. Thus, there is
compatibility with existing semiconductor and photonic substrate
materials.
[0101] 9. Modified DNA polymers can be used to form
three-dimensional structures, thus leading to ultra high density
secondary storage schemes.
[0102] 10. DNA polymers can be reversibly assembled and
disassembled by cooling a nd heating, or modified to remain in the
assembled state. This is a critical property for self-organizing
materials as it allows for more options in the manufacture of
resulting systems.
[0103] 11. The structural and organizational properties of DNA
polymers (nucleic acids in general) are well understood and can be
easily modeled by simple computer programs. Thus, more complex
molecular photonic and electronic devices can be designed.
DETAILED DESCRIPTION OF THE INVENTION
[0104] This invention relates to methodologies, techniques, and
devices which utilize self-assembling DNA polymers, modified DNA
polymers, DNA derivitized structures and other affinity binding
moieties for nanofabrication and microfabrication of electronic and
photonic mechanisms, devices and systems. This invention also
relates to processes which allow mutiplex and multi-step
fabrication, organization or assembly of modified DNA polymers, DNA
derivitized structures, and other types of affinity or charged
structures into more complex structures on or within silicon or
other surfaces.
[0105] For purposes of this invention "DNA polymers" is broadly
defined as polymeric or oligomeric forms (linear or
three-dimensional) of nucleic acids including: deoxyribonucleic
acid, ribonucleic acids (synthetic or natural); peptide nucleic
acids (PNA); methyphosphonates; and other forms of DNA in which the
backbone structure has been modified to produce negative, positive
or neutral species, or linkages other than the natural phosphate
ester. Also included are forms of DNA in which the sugar or base
moieties have been modified or substituted, and polymeric forms of
DNA in which nucleotide or polynucleotide units are interspersed
with other units including but not limited to phosphate ester
spacer moieties, amino acids, peptides, polysaccharides, synthetic
organic polymers, silicon or inorganic polymers, conductive
polymers, chromophoric polymers and nanoparticles or
nanostructures.
[0106] For purposes of this invention "Modified or Derivitized DNA
polymers" are broadly defined as nucleic acids which have been
functionalized with chemical or biological moieties (e.g., amines,
thiols, aldehydes, carboxyl groups, active esters, biotin and
haptens) which allow the DNA to be attached covalently or
non-covalently to other molecules, structures, or materials. Also
included are forms of DNA which have been modified or Derivitized
with chromophores, fluorophores, chelates, metal ions, amino acids,
peptides, proteins, enzymes, antibodies, or aliphatic or aromatic
moieties which change solubility, and moieties which change the net
charge on the DNA molecule.
[0107] For purposes of this invention "DNA Derivitized structures"
are broadly defined as nanostructures (organic, inorganic,
biological); nanoparticles (gold, silica, and other inorganic
materials); organic or polymeric nanobeads; submicron devices,
components, particles, (silicon based devices produced by
photolithography or E-beam lithography); and micron scale devices
or particles which have been functionalized with a specific DNA
sequence which allows the structure to be specifically attached or
interconnected to another structure, device, or to a specific
location on a surface.
[0108] While the terms "nanostructure" refers to sub-micron sized
structures, terms such as "nano" or "micro" are not intended to be
limited in the sense that a micron scale device can be
functionalized with DNA polymers which technically have lengths of
10-180 nanometers.
[0109] The unique properties of DNA provides a programmable
recognition code (via the DNA base sequence) which can be used for
specific placement and alignment of sub-micron and nanoscale
structures. The basic chemistry and technology required to attach
specific DNA sequences to organic, semiconductor, and metallic
compounds is known to the art and specific chemistries are
described for carrying out such applications.
[0110] In the preferred embodiment, the process by which photonic
devices are aligned and fixed to substrate surfaces, involves first
coating them with a specific DNA polymer sequences. The area of the
host substrate where attachment of the specific device is desired,
would then be coated with the specific complementary DNA sequence.
The substrate would be exposed to a solution containing the DNA
covered devices, and hybridization between complementary DNA
strands allowed to occur. This hybridization process effectively
grafts the devices to their proper receptor locations on the
substrate surface. This self-assembly fabrication process can be
used for, by way of example, (1) the fabrication of light emitter
arrays over large surface areas, and (2) the fabrication of two or
three-dimensional photonic band-gap crystal structures.
[0111] This fabrication technique has major applications in the
field of optoelectronics and in the manufacturing of various
hybrid-integrated components including flat panel displays, medical
diagnostic equipment and data storage systems. Novel devices with
very small physical dimensions take advantage of various quantum
confinement techniques. In most cases, these devices are preferably
distributed over large areas (e.g. smart pixels and displays).
Other devices may be brought together in dense regular crystal
lattices (e.g. photonic bandgap crystals). In both cases, the
physics of the devices are now understood, and viable fabrication
techniques of these inventions are required. With regard to new
processing techniques, DNA self-assembly technology allows these
devices to be constructed.
[0112] Integrated photonic and electronic systems utilize the
inventive fabrication technologies including nanostructure
fabrication, integration, interconnection and self-assembly
techniques. For such applications, DNA self-assembly fabrication
technology involves the following steps. Synthetic DNA polymers are
designed with highly specific binding affinities. When covalently
attached to nanoscale organic, metallic or semiconductor component
devices, DNA polymers provide a self-assembly fabrication
mechanism. This mechanism can be used for both the selective
grafting of devices to specific pre-programmed locations on a
desired surface, and for the clustering of devices into
pre-programmed 2 and 3 dimensional lattices.
[0113] For grafting an array of photonic component devices onto a
host substrates, DNA polymers with complementary sequences are
first synthesized as shown in FIG. 2. The photonic component
devices and desired areas of the host substrate (receptor areas)
are coated with the complementary DNA sequences. The host substrate
is then introduced into a hybridization solution. The devices
coated with the specific DNA polymers are also released from their
mother substrate into the solution. The released devices can be
actively transported to their receptor areas under the influence of
electrically or optically induced local fields (electrophoresis).
Hybridization is carried out by carefully controlling the solution
temperature, ionic strength, or the electric field strength. Once
the devices are grafted via hybridization to their specific
receptor areas, the solution is removed and the substrate is dried.
Metallurgical (or eutectic) bonding can now be carried out at a
higher temperature to fully bond the devices to the host substrate
material. The clustering of sub-micron and nanoscale elements into
2-D or 3-D structures (e.g., photonic band-gap crystals), can be
carried out in a similar fashion. In this case, the host substrate
is replaced by other nanoscale elements. A major difference
however, is the attachment technique used to position different DNA
strands on the nanoscale elements.
[0114] The self-assembly fabrication technique based on DNA
polymers offers two unique features. First, by removing the
requirement for conservation of relative device spacing (as defined
by the mother substrate) during the device grafting (hybridization)
process, the technique enables the micron, sub-micron or nanoscale
devices to be fabricated densely on their mother substrates and
then be redistributed in a preprogrammed fashion onto the host
substrate (FIG. 3.a).
[0115] This feature has a profound impact on the viability of
intra-chip optical interconnects within large chips. It lowers the
cost of silicon based smart pixels where photonic devices must be
fabricated on more expensive smaller substrates. The second feature
is the ability to manipulate and orient with respect to each other
a large number of nanoscale devices (e.g. organic or metallic
nanospheres). This feature allows the "growth" of synthetic
photonic crystals with large lattice constants possessing desired
orientation symmetries for exhibiting photonic bandgap properties
(FIG. 3.b).
[0116] Thus, the highly specific binding affinities and
self-assembly of DNA polymers can lead to:
[0117] (1) Low cost smart pixels and display devices by enabling
photonic or electronic micron or nanoscale devices to be
self-assembled and integrated over very large areas of silicon or
other substrates, i.e. the self-assembly of an arrays of light
emitters on a silicon substrate,
[0118] (2) Highly selective wavelength and tunable devices by
enabling dielectric nanostructures to be self-assembled to form
photonic bandgap crystals, i.e. the encapsulation of emitter
devices within a photonic bandgap crystal layer created by the
self-assembly of DNA nanospheres,
[0119] (3) Ultra high density optical storage media by enabling
chromophore molecules and nanostructure units to be selectively
self-positioned, and
[0120] (4) The selective positioning of bonding structures, such as
gold, tin or solder structures as bonding pads, e.g., to achieve
low cost or unassisted die-to-die processing, e.g., for flip-chip
applications.
[0121] In the preferred embodiment, these applications require four
steps in the process. The first involves the design and synthesis
of the DNA polymer sequences and their selective attachment to the
sub-micron and nanoscale devices of interest. Second, attachment of
specific complementary DNA polymers to pre-selected receptor
locations on a host substrate surface. Third, the self-assembly of
the devices by the DNA hybridization process. The fourth process
involves establishing the electrical contacts.
[0122] This invention brings together molecular biological (DNA
structure and function) and photonic and electronic device
principles in a synergistic manner. On the photonic device side,
novel devices with very small physical dimensions take advantage of
various quantum confinement techniques. In most cases, these
devices must be distributed over large areas (e.g. smart pixels and
displays). In other cases, these devices must be brought together
densely to form regular crystal lattices (e.g. photonic bandgap
crystals). With regard to processing techniques, self-assembly DNA
techniques with its well developed base of DNA synthesis,
modification, and hybridization is an enabling technology for these
applications. DNA linkage to solid supports and various other
materials is possible via a variety of processes for attaching DNA
selectively to silicon, gold, aluminum and other inorganic and
organic materials. A number of thin film processing techniques are
highly complementary with these DNA processes. For example, as will
be described later, the lift-off process can be easily adapted to
produce micron, and sub-micron devices with attached DNA
sequences.
[0123] Key Processes for DNA Based Component Device
Self-Assembly
[0124] Four techniques are important for the DNA based component
device self-assembly process. These are the DNA polymer synthesis,
DNA attachment chemistry, DNA selective hybridization and epitaxial
lift-off of semiconductor thin films and devices. In the following
sections we provide brief summaries of these techniques.
[0125] DNA Synthesis and Derivitization
[0126] The synthesis of the DNA polymer or oligomer sequences,
their purification, and their Derivitization with the appropriate
attachment and chromophore groups can be carried out in the
following preferred manner: DNA sequences are synthesized using
automated DNA synthesizer and phosphoramidite chemistry procedures
and reagents, using well known procedures. DNA polymers
(polynucleotide, oligonucleotides, oligomers) can have primary
amine groups incorporated at chemical bonding sites for subsequent
attachment or functionalization reactions. These primary amine
groups can be incorporated at precise locations on the DNA
structure, according to the need for that particular sequence.
Attachment sequences can also contain a terminal ribonucleotide
group for subsequent surface coupling reactions. Sequences,
including the amino modified oligomers, can be purified by
preparative gel electrophoresis (PAGE) or high pressure liquid
chromatography (HPLC). Attachment sequences with terminal amino
groups can be designed for covalent bonding to gold, silver, or
aluminum metalized features or to small areas where silicon dioxide
is present. These sequences can be further Derivitized with a
thiolation reagent called succinimidyl
3-(2-pyridyldithio)propionate (SPDP). This particular reagent
produces a sequence with a terminal sulfhydryl group which can be
used for subsequent attachment to metal surfaces. Other attachment
sequences containing a terminal ribonucleotide group can be
converted to a dialdehyde derivative via Schiffs base reaction.
These attachment sequences can then be coupled to aminopropylated
silicon dioxide surfaces. Specific sequences designed for
electronic or photonic transfer responses can be functionalized
with their appropriate chromophore, fluorophore, or charge transfer
groups. Many of these groups are available off-the-shelf as
activated reagents that readily couple with the chemical bonding
sites described above to form stable derivatives.
[0127] DNA Attachment to Solid Supports and Preparation of the Host
Substrate Materials
[0128] This step involves the covalent coupling of the attachment
sequences to solid support materials. In the general area of DNA
attachment to solid materials, sequences have been covalently
attached to a number of materials which include: (i) Glass
(SiO.sub.2), (ii) Silicon (Si), (iii) Metals (Gold, Silver,
Aluminum), and (iv) Langmuir-Blodgett (LB) films. Glass, silicon,
and aluminum structures have been prepared in the following manner.
Glass and silicon (SiO.sub.2) are first treated with dilute sodium
hydroxide solution and aluminum with dilute hydrogen fluoride
solution. The materials are then Derivitized for covalent coupling
with the attachment sequences by treatment with
3-aminopropyltriethoxysilane (APS). This is carried out by
refluxing the materials for 2-5 minutes in a 10% APS/toluene
solution. After treatment with APS, the materials are washed once
with toluene, then methanol, and finally dried for 1 hour at
100.degree. C. Attachment to the APS Derivitized materials is
carried out by reaction with the specific dialdehyde Derivitized
attachment oligomers (see FIG. 4) for 1-2 hours in 0.1 M sodium
phosphate buffer (pH 7.5). In addition, attachment to metal (gold,
silver, aluminum) and organic features can be carried out.
[0129] To delineate the areas where the grafting of the specialty
devices will take place, a selective attachment procedure for the
complementary DNA polymer may be carried out. The selective
attachment can be realized by using the inherent selectivity of DNA
sequences, selective attachment chemistries, or by directed
electrophoretic transport. Alternatively after attachment, the DNA
strands in unwanted regions can be destroyed by UV radiation. This
approach is useful only when one group of devices need to be
self-assembled. This approach would in normal operation preclude
subsequent DNA attachment processes, and would not allow for the
self-assembly of several specialty device groups. Attachment
chemistry is strongly dependent upon the materials used to which
the DNA polymers may be attached.
[0130] For example, to attach DNA to aluminum pads on a silicon
chip coated with a protective glass layer, the aluminum regions are
activated by dipping the sample for a short period of time into a
dilute buffered HF solution. The end result of this process is that
only a few DNA strands are attached to the protective glass layer
while the exposed aluminum pads are highly reactive to DNA. This
material selectivity is a convenient and general way to attach DNA
to the desired regions. When material selectivity is combined with
UV directed inactivation and electrophoretic transport, this allows
for repeatable attachment processes to be carried out
sequentially.
[0131] Consider the simultaneous self-assembly of several types of
specialty devices. The receptor pads need to be grouped according
to the device to which they are to be coupled. In this case, each
pad group needs to be coated with a specific DNA sequence
complementary to the DNA sequence attached to the specialty device
that it would be bonded to. In order to "pre-program" the receptor
pads, each DNA sequence is attached sequentially to the proper
pads. This can be easily achieved by using the electrophoretic
transport process and by applying a negative potential to the pads
where DNA attachment is not desired. Simultaneously, a positive
voltage can be applied to enhance attachment to the desired
locations. Alternatively, an optically induced electric field can
be used to migrate the DNA strands to desired locations. For a
second set of DNA sequence attachment, the procedure is repeated.
It should be pointed out that when only one type of device needs to
be self-assembled on the host substrate, the use of the material
selectivity of the DNA attachment chemistry alone is sufficient. UV
radiation of the regions where DNA hybridization is not desired,
would be carried out.
[0132] Component Device Preparation and Epitaxial Lift-Off
[0133] Another key step for the self-assembly process is the
preparation of the sub-micron and micron-scale component devices
for DNA attachment, their handling during the attachment process,
and their final release into solution prior to hybridization. The
epitaxial lift-off (ELO) process can substantially improve these
aspects of this technique. Epitaxial films in the thickness range
of 20 nm to 10 mm have been separated from their growth substrates,
handled and manipulated. For example, using this technique thin
III-V semiconductor films have been direct-bonded to foreign
substrates, such as processed silicon wafers. Prior to lift-off,
various devices can be fabricated on the films while still on their
mother substrates. The first step in our self-assembly technique is
the preparation of the photonic devices that are to be grafted.
FIG. 5 describes a preferred process flow for this preparation
step. The photonic devices are fabricated in a standard fashion on
their mother substrates on a sacrificial layer as required by the
ELO process. A suitable coating layer is then deposited on these
devices. By controlling the characteristics of the deposited
material with respect to device materials the behavior of the
devices once released into the saline solution can be controlled.
For example, by controlling the coating material properties the
direction of the devices in the solution can be controlled. A thick
polyimide film is spun to provide a physical support to the devices
after the ELO process. The ELO process is carried out and the thin
film devices are separated from their mother substrates. By using
plasma etching, the polyimide holding membrane is recessed in areas
with no devices. If needed, a metal layer can be deposited to
assure good electrical contacts to the photonic devices. The DNA
attachment process is then carried out and a specific DNA sequence
is covalently attached on all metal surfaces. By irradiating the
front surface with a UV light, the photonic devices are used as a
self-aligned mask enabling exposure of polyimide areas coated with
DNA polymer. In these areas, the DNA polymers react to a form that
is not suitable for further hybridization. By using a solvent, the
polyimide may then be removed and the devices released into the
saline solution used for the further hybridization processes.
[0134] Selective DNA Hybridization Techniques
[0135] Once the host substrate is pre-programmed and the component
devices are released into the solution, the self-assembly process
can take place. Two different approaches for hybridization are
applicable: (1) Conventional hybridization and (2) Active
hybridization using an electric field.
[0136] For the conventional hybridization process, all devices may
be released simultaneously into the solution. By gently agitating
the devices in the solution at the proper hybridization stringency
temperature and ionic strength, hybridization of the complementary
DNA strands takes place as the proper device-receptor pairs come
into contact. The probability of hybridization taking place may be
related directly to the probability of the proper device-host pad
pairs coming into contact. Since the probability distribution is
most likely random, this process may take longer to achieve
reasonable hybridization yields on large area surfaces unless the
solution is saturated with the devices. In order to improve the
selectivity and alignment accuracy several controlled heating and
cooling cycles may be carried out during the hybridization process.
During the heat cycle, weakly hybridized components are dissociated
away to increase the chances of forming stronger bonds.
[0137] For active or electronic hybridization, the host itself or
another electrode array manufacturing device are used to produce
localized electric fields which attract and concentrate selected
component devices at selected locations. For this process the host
or manufacturing device has sites which can be used as an
electrodes. A potential is applied across the solution between
selected receptor sites and auxiliary electrodes. Receptor sites
biased opposite (+) to the net charge (-) on selected devices, now
affect the electrophoretic transport and concentration of these
devices thereby increasing the rate of hybridization and binding.
These sites can be selectively switched on or off using electronic
or photonic addressing. A pulsing DC or biased AC electric field
can be applied at a suitable frequency to eliminate the screening
effect of the unwanted device types.
[0138] The electric field effect can also be used in a protective
manner. In this case, the receptor pads are now biased the same (-)
as the net charge (-) on the devices. The devices are then repelled
from these regions and interact or bind only to those locations
which have the opposite charge (+) or are neutral. Active electric
field transport can be used to carry out multiplex and multi-step
addressing of component devices and structures to any location on
the host array.
[0139] Another important consideration during hybridization is the
alignment accuracy of the photonic devices on the host substrate.
It is assumed cylindrical photonic devices that rotation is
invariant. In this case, if the device and host pad diameter is d,
an alignment accuracy of d/2 may be first achieved with the natural
hybridization process prior to the drying process. Devices that are
mis-aligned with more than d/2 misalignment will not form a strong
bond during the hybridization process and will not be held in place
during the heating and cooling cycles of the hybridization process.
Better alignment accuracy and orientation are possible when active
electric field hybridization is used. Once the substrates are
removed from the solution, increased surface tension during the
drying process could further improve the alignment accuracy.
[0140] Metallurgical Bonding
[0141] After the hybridization process the specialty devices are
held in their proper places through the formation of the
double-stranded DNA structure which has a very high bonding
strength. The entire assembly is then cleaned by rinsing and then
dried. The DNA bond strength remains in the solid state and serves
to keep the devices in place. At this point of the process, there
is however, no electrical contact between the host substrate and
the photonic devices. One method to achieve a metallurgical bond
exhibiting an ohmic contact between the host substrate and the
photonic devices is to use conductive materials on the pads and
devices that can be bonded together eutectically at low
temperatures. A second method is to use metals with low melting
temperatures like solder or indium under a metal layer that is
active for DNA attachment. While the photonic devices are held in
place by the DNA bonds, the application of heat will result in the
formation of a metallurgical bond. The DNA polymer will
disintegrate within the bond but may only contribute to an
increased contact resistance depending on the initial DNA loading
factor used.
[0142] Development of Self-Assembled Emitter Arrays
[0143] As one example of the utility of these inventions, emitter
arrays can be advantageously formed. Specific DNA polymer sequences
may be covalently attached to semiconductor light emitting diodes
(LED) and the complementary DNA sequences may be attached to
receptor pads on the host silicon substrate. UV/DNA patterning
techniques may be used for selective activation/inactivation of DNA
on the coated surfaces. All DNA Derivitized test structures and
materials will then be tested for selective hybridizability using
complementary fluorescent DNA probes. LED test devices Derivitized
with specific DNA sequences may be hybridized to test substrates
Derivitized with complementary DNA sequences.
[0144] Development of Self-Assembled Photonic Band-Gap
Structures
[0145] Photonic or crystals may be formed using the DNA
self-assembly technique. Photonic Bandgap Structures are artificial
periodic lattice structures in two- or three-dimensional
arrangements and composed of elements of proper dimensions, density
and separations. Such structures result in the modification of
photonic density of states and a gap in the electromagnetic wave
dispersion. Indeed, photonic bandgap structures operating at
specific optical wavelengths have been demonstrated. Potential
applications of photonic bandgap materials include tailoring of the
spontaneous emission of a laser to achieve ultra-low threshold
lazing, improved wave guiding structures without radiation loss,
novel optical modulators, etc.
[0146] In one aspect of these inventions, nano-scale rods or
spheres of higher dielectric constant are positioned in a medium of
lower dielectric constant. A three-dimensional diamond lattice
arrangement of close-packed tetrahedrally-connected dielectric
spheres (200 nm in diameter and a refractive index of 3.6) embedded
in a lower-dielectric-constant medium such as air exhibits photonic
bandgaps. This invention relates to new ways of constructing
photonic crystals by self-assembling high dielectric constant
elements with desired geometry's in lower dielectric materials. In
order to construct such a structure and to obtain the desired
lattice geometry and nano-elements at the lattice sites, the
selective attachment of DNA sequences to the nano-elements and the
hybridization of finite sequences of DNA strands are employed.
Metal spheres exhibiting magnetic properties may have attached DNA
strands. Magnetic properties may be used to control the orientation
of the spheres (or rods for 2-D crystals). The metal spheres may be
dipped into a DNA solution, aligned using a magnetic field, and
exposed under UV radiation. This technique allows 2D and 3D
photonic-bandgap structures to be "grown" around active
optoelectronic devices with minimum fabrication complexity.
Additionally, because the DNA bonds connecting the nanospheres are
somewhat flexible, this technique may also provide a means of
realizing tunable photonic bandgap structures. The process for
electronic orientation is discussed in the "Process for Electric
Field Orientation Synthesis of Nanospheres and Sub-Micron Devices",
below.
[0147] The various DNA polymer (oligonucleotide) sequences
described above, in the 20-mer to 50-mer size range, may be
synthesized on automated DNA synthesizers using phosphoramidite
chemistry. Longer DNA sequences are generally required to bind
larger objects to surfaces because the binding force must be
sufficient to overcome forces (e.g., shearing forces) tending to
remove the object. Longer DNA sequences (>50 mers) may be
constructed using the polymerize chain reaction (PCR) technique.
The DNA sequences may be further Derivitized with appropriate
functional groups (amines, thiols, aldehydes, fluorophores, etc.).
All sequences may be purified by either PAGE gel electrophoresis or
HPLC. After purification, all sequences may be checked on
analytical PAGE gels for purity, and then tested for specificity by
hybridization analysis.
[0148] Several DNA sequences may be used to develop and test
additional chemistries for the covalently attachment to various,
organic polymer based nanospheres, semiconductor, and other
material substrates (glass, gold, indium tin oxide, etc.).
Additional attachment chemistries provide more options and
flexibility for attachment selectivity to different semi-conductor
materials.
[0149] Specific DNA polymer sequences may be covalently attached to
semi-conductor test structures and the complementary DNA sequences
to test substrate (host) materials. UV/DNA patterning techniques
may be used for selective activation/inactivation of DNA on the
coated surfaces. All DNA Derivitized test structures and materials
will then be tested for selective hybridizability using
complementary fluorescent DNA probes.
[0150] Nanospheres, nanoparticles, and semi-conductor test
structures Derivitized with specific DNA sequences will now be
hybridized using both conventional (temperature, salt, and
chaotropic agents) and electronic (electrophoretic) techniques to
the test substrates (hosts) Derivitized with complementary DNA
sequences. The hybridization techniques may be optimized for
highest selectivity and least amount of non-specific binding.
[0151] Fabrication of an LED Array
[0152] Specific DNA polymer sequences may be covalently attached to
semi-conductor light emitting diode (LED) component devices and the
complementary DNA sequences to host materials. UV/DNA patterning
techniques may be used for selective activation/inactivation of DNA
on the coated surfaces. LED component devices Derivitized with
specific DNA sequences are then hybridized to test substrates
(hosts) derivitized with complementary DNA sequences.
[0153] Self-Assembly Fabrication of a Photonic Crystal
Structure
[0154] Multiple specific DNA polymer identities may be incorporated
into nanoparticles or nanospheres for the self-assembly around
emitter test devices located on motherboard materials. UV/DNA
patterning techniques may be used for selective
activation/inactivation of DNA on the coated surfaces.
Nanoparticles Derivitized with specific DNA sequences will now
hybridized to the emitter test devices located on the substrates
(hosts) derivitized with complementary DNA polymers.
[0155] Further Aspects of Self-Assembly
[0156] This invention provides for assembling specialty devices in
parallel and over larger areas (up to several meters on a side)
using a "self-assembly" technique. In this approach, each device to
be grafted somehow "knows" where it is destined to be on the host.
This invention relates to a new integration technique based on
programmable self-assembly principles encountered in biological
systems. This new technique removes the requirement of dimension
conservation during the grafting process. Our objective is to
demonstrate the self-assembly of micro/nano structures on silicon
using DNA (Deoxyribonucleic Acid) polymers as "selective glues",
thereby developing techniques for integrating these structures
sparsely onto large area hosts. This brings together with high
precision, at low cost, devices made of different materials with
different real densities as shown in FIG. 30. This approach relies
on the principles of programmable self-assembly found in all
biological systems, and uses existing well-understood synthetic DNA
chemistry as the enabling process. These techniques include: 1)
remove the specialty devices from their mother substrates using the
epitaxial lift-off process, 2) attach selective DNA polymer
sequences onto the specialty devices using DNA attachment chemistry
specially developed in our company, 3) selectively attach
complementary DNA polymer sequences to proper locations on the host
substrate, and 4) carry out self-assembly by using hybridization of
the complementary DNA strands. This uses DNA polymer sequences as a
smart and very selective glue to attach micron/nanosize specialty
devices to designated areas on a motherboard (see FIG. 31).
[0157] Selective DNA Hybridization and Electric Field Transport
Techniques
[0158] Techniques for the hybridization of DNA sequences to
complementary DNA sequences attached to solid support materials are
well known and used in many biotechnological, molecular biology,
and clinical diagnostic applications. In general hybridization
reaction are carried out in aqueous solutions which contain
appropriate buffer electrolyte salts (e.g., sodium chloride, sodium
phosphate). Temperature is an important parameter for controlling
the stringency (specificity) and the rate of the hybridization
reactions. Techniques exist for hybridization of DNA sequences to
semiconductor materials. The first is a UV lithographic method
which allow imprinting or patterning of DNA hybridization onto
solid supports materials such as silicon dioxide and various
metals. The second is a method for electrophoretically transporting
DNA-nanostructures (nanostructures to which specific DNA sequences
are attached) to selected locations on substrate materials. The
technique for UV lithography with DNA involves first coating a
substrate material with a molecular layer of specific attachment
DNA polymer sequences. An appropriate mask can be used to imprint a
pattern into the attachment layer of DNA by exposure to UV
irradiation (300 nm) for several seconds. The DNA in the area on
the substrate exposed to UV light becomes in-active to
hybridization with its complementary DNA sequence i.e., it is not
able to form the double-stranded structure. FIG. 7 show fluorescent
DNA on a silicon structure was patterned with 10 micron lines using
an electron microscope grid pattern. After UV patterning the
material is hybridized with a complementary fluorescent labeled DNA
probe, and examined epifluorescent microscopy. The fluorescent
image analysis shows where the complementary probe has hybridized
(fluorescent), and where no hybridization has occurred (no
fluorescence). In addition to DNA based UV photolithographic type
processes, other electric field based process allows derivitized
DNA and charged fluorescent nanospheres to be electrophoretically
transported and deposited onto selective microscopic locations on
solid supports. The basic method and apparatus for this technology
is shown in FIG. 32. Negatively charged DNA, sub-micron or
micron-scale structures can be suspended in aqueous solutions and
transported via an electric field (electrophoresis in solutions) to
microscopic locations which are biased positive, relative to other
locations which are biased negative. This is a particularly
important technique in that it provides a mechanism to direct the
transport of specifically labeled devices to specific locations on
a substrate material.
[0159] Micron/Nanoscale Structure Preparation
[0160] The first step in our self-assembly technique is the
preparation of the specialty devices to grafting. In this case, the
specialty devices are fabricated in a standard fashion on their
mother substrates on a sacrificial layer as required by the ELO
process. A suitable coating layer is then deposited on these
devices to assure they have a Brownian like motion in the saline
solution. By controlling the characteristics of the deposited
material with respect to device materials the behavior of the
devices once released into the saline solution can be controlled.
For example, by controlling the coating material properties we
could control the direction of the devices in the solution. Once
the devices are coated, a thick polyimide film may be spun to
provide a physical support to the devices after the ELO process.
The ELO process may be carried out and the thin film devices may be
separated from their mother substrates. By using plasma etching the
polyimide film may be recessed to provide sufficient steps to
prevent the metal layer from being continuous. The DNA attachment
process is then carried out and a specific DNA sequence may be
covalently attach on all the metal surfaces. By irritating with a
UV light from the front surface of the devices, the DNA areas that
are exposed and not protected, may be destroyed or put in a form
that is not suitable for further hybridization. By using a proper
solvent the polyimide will then be removed and the devices may be
released into the saline solution used for the further
hybridization processes.
[0161] Preparation of the Motherboard Substrate
[0162] To delineate the areas where the grafting of the specialty
devices will take place, a selective attachment procedure for the
complementary DNA polymer must be carried out. The selective
attachment can be realized by using the inherent selectivity of DNA
sequences, selective attachment chemistries, or by directed
electrophoretic transport. Alternatively after attachment, the DNA
strands in unwanted regions can be destroyed by UV radiation. This
approach is useful only when one group of devices need to be
self-assembled.
[0163] As described in earlier sections, DNA attachment chemistry
is strongly dependent on the materials used to which the DNA
polymers may be attached. For example, to attach DNA to aluminum
pads on a silicon chip coated with a protective glass layer, we
first activate the aluminum regions by dipping the sample for a
short period of time into a dilute buffered HF solution. The end
result of this process is that only a few DNA strands are attached
to the protective glass layer while the exposed aluminum pads are
highly reactive to DNA. This material selectivity is a convenient
and general way to attach DNA to the desired regions. When material
selectivity is combined with UV directed inactivation and
electrophoretic transport process, this allows for repeatable
attachment processes to be carried out sequentially. Consider the
simultaneous self-assembly of several types of specialty devices.
The pads need then to be grouped according to the device to which
they are to be coupled. In this case, each pad group needs to be
coated with a specific DNA sequence complementary to the DNA
sequence attached to the specialty device that it would be bonded
to. In order to "pre-program" the host pads, each DNA sequence can
be attached sequentially to the proper pads. This can be easily
achieved by using the electrophoresis process and by applying a
negative potential to the pads where DNA attachment is not desired.
Simultaneously, a positive voltage can be applied to enhance
attachment to the desired locations. For a second set of DNA
sequence attachment, the procedure may be repeated with a different
set of programming voltages. Thus, when the self-assembly of
multiple device types need to be carried out simultaneously, the
host board receiving pads may be programmed by applying a proper
set of positive and negative potentials to the pads. When only one
type of device needs to be self-assembled on the host board, the
use of the material selectivity of the DNA attachment chemistry
alone is sufficient.
[0164] Specific DNA Polymers: A Selective Glue
[0165] Once the host board is pre-programmed and the specialty
devices are released and are freely moving in the saline solution
bath, the self-assembly process can take place. At the proper
(hybridization) stringency temperature, and by agitating gently the
devices in the solution, hybridization of complementary DNA strands
may be allowed to take place as the proper device-pad pairs come
into contact (see FIG. 33). To achieve this process several
different methods may be investigated.
[0166] Conventional and Electronic Hybridization
[0167] In this methods all devices may be released simultaneously
into the solution, and the probability of a hybridization process
taking place may be related directly to the probability of the
proper device-pad pairs to come into contact. Under very
simplifying assumptions, the probability of a hybridization Ph may
be roughly related to the ratio of the total available pad area
A.sub.p to the mother board area A.sub.mb
P.sub.h.varies.NA.sub.p/A.sub.mb
[0168] where N is the real density of one of the specialty device
groups in the solution. Since the probability distribution is
expected to be random, this process may take very long times to
achieve reasonable hybridization yields. Alternatively it may
require the solution to be saturated with the specialty devices.
This may increase the cost of the process and limit the number of
types of specialty devices that can be self-assembled. In order to
improve the selectivity and alignment accuracy several heating and
cooling cycles will be carried out during the hybridization
process. During the heat cycle, weakly hybridized components may be
dissociated away to increase the chance of forming stronger
bonds.
[0169] Epitaxial Lift-Off Process
[0170] A key part of the self-assembly process is the preparation
of the micro/nano scale devices for DNA attachment, their handling
during the attachment and finally their release into the saline
solution prior to hybridization. The most popular ELO approach is
to employ the selectivity of dilute HF acid on the Al GaAs series
of alloys. The Aluminum rich alloys etch at a rate of approximately
1 mm/hr, while the etch rate of Gallium rich alloys is almost
undetectable, less than 0.1 nm/hr. An intermediate layer of AlAs
dissolves, allowing upper epitaxial layers to simply float away
from the substrate. Other separation methods have also been used,
including mechanical cleavage (CLEFT), and total substrate etching
down to an etch stop layer. Epitaxial films in the thickness range
between 20 nm and 10 mm have been separated from their growth
substrates, handled and manipulated.
[0171] For example, using this technique thin III-V semiconductor
films have been direct-bonded to foreign substrates, such as
processed silicon wafers. The mechanical flexibility of ELO films
allows a perfect conformation of the films to the substrate
topography, which creates a strong and complete bond. The ELO
technique then, produces a monolithic-like epitaxial thin film on
an engineered substrate. Prior to lift-off, various devices can be
fabricated on the films while still on their mother substrates. The
ELO technique stands somewhere intermediate between a hybrid
approach, such as flip-chip solder bump mounting, and a fully
monolithic approach, such as direct hetero-epitaxy; it combines,
however, the advantages of both. ELO is a true thin-film
technology, allowing thin-film metal wiring which passes back and
forth over the edge of a thin III-V film and onto a silicon
micro-chip substrate. At the same time, the thin film is grown
lattice-matched and essentially homo-epitaxially. Material quality,
of the utmost importance for minority carrier devices such as light
emitters, is never compromised. Advantages of the ELO technology
over hybrid flip-chip technology include low packaging capacitance
and high packing density. For high speed micro-circuits, wiring
capacitance must be very low. The penalty is not merely the burden
of added power dissipation. Since the series resistance of metal
interconnects is not negligible, the RC time constant will
ultimately act to limit the speed of opto-electronic micro-circuits
irrespective of power dissipation problems, severe as they might
be. The ultimate achievable packing density is somewhat scaled with
respect to the working dimension of technologies. Therefore, the
ELO may offer more in this aspect than the solder bump
technique.
[0172] ELO films grafting on processed silicon micro-circuits
requires consideration of the ultra-fine scale roughness of the
deposited oxide surfaces of the micro-chip. Surface roughness
interferes with the quality of the Van der Waals or metallurgical
bond.
[0173] Sequential Hybridization Under DC Electric Field
[0174] To increase the probability of hybridization, a second
method is to introduce each device group separately and to confine
the specialty devices within regions near the positively biased
pads. This confinement can be done under the influence of a DC
electric field by applying a suitable positive voltage to the pads.
The effect of the electric field can then be viewed as increasing
the ratio of the areas, or equivalently increasing the device
density, N, in the above equation. However, in this case each
device group must be introduced sequentially, so the unwanted
device groups do not screen the right devices from reaching the
pad.
[0175] Parallel Hybridization Under an AC Electric Field
[0176] The disadvantage of the sequential hybridization is that it
increases the cost of manufacturing as the types of specialty
devices is increased. An alternative method is to introduce all
device types concurrently into the solution, to apply an initial DC
voltage to create a distribution of the devices around each pad,
and then to apply an AC voltage at a suitable frequency to
eliminate the screening effect of the unwanted devices types. The
effect of the AC field can be seen as a stronger stirring
mechanism.
[0177] Metallurgical Bonds
[0178] After the hybridization process the specialty devices are
held in their proper places through the formation of the
double-stranded DNA structure which has very high bonding strength.
The entire assembly is then cleaned by rinsing and then dried. At
this point there is no electrical contact between the host board
and the specialty devices. The DNA bond strength remains in the
solid state and serves to keep the devices in place. One method to
achieve a metallurgical bond with ohmic contact is to use
conductive materials on the pads and devices that can be bonded
together eutectically at low temperatures. A second method is to
use metals with low melting temperatures like solder or indium
under a metal layer that is active for DNA attachment. In this case
the bumps must be made in nanometer dimensions. While the device
are held in place by the DNA bonds, in both cases the application
of heat will result in the formation of a metallurgical bond and an
ohmic contact. The DNA polymer will remain within the bond but may
only contribute to an increased contact resistance depending on the
initial DNA loading factor used. FIG. 34 shows a the process
described above.
[0179] Alignment and Orientation of the Specialty Devices
[0180] One of the critical issues that needs to be addressed in the
self-assembly approach is the accuracy with which the specialty
devices can be aligned to the pads on the host board. We will first
assume that the specialty devices have a circular base such that
the process is rotation invariant. In this case, it is expected
that if the pad diameter is d, an alignment accuracy of d/2 could
be achieved with the DNA bonding process. Devices that are
misaligned with more than d/2 misalignment will not form a strong
bond during the hybridization process and would not be held in
place during the heating and cooling cycles of the hybridization
process. In addition, if the nano-bump technology outlined in the
previous section is employed, after the high temperature cycle for
forming the metallurgical bonds, the devices may be self-aligned to
the pads in a similar fashion as with the C4 technology used for
flip-chip bonding.
[0181] A more difficult issue arises if the specialty device do not
have a circular symmetric base and need to be placed with a certain
orientation on the pads. Two different approaches for bonding with
the proper orientation may be used. As a first approach, properly
patterned silicon dioxide layers are used to physically mask out
specialty devices with the wrong orientations as shown in FIG. 35.
The devices will fit onto the pads only if they possess the right
orientation. Another approach to orient the device is to use
coulombic forces prior to the hybridization of DNA. By ion
implantation, or e-beam lithography exposure an opposite sign
charge build-up can be realized in certain locations on the pads
and on the devices. These charge patterns guide the devices to
their proper orientations. As can be seen in FIG. 35, both
approaches can be used together to provide DNA bonding with proper
orientation of the specialty devices.
[0182] Process For Electric Field Orientation Synthesis of
Nanospheres and Sub-micron Devices
[0183] Electric field synthesis is preferably used for producing
nanostructures or microstructures (e.g., nanospheres,
nanoparticles, sub-micron and micro scale devices) with multiple
DNA surface identities. These multiple surface identities can be in
the form of specific DNA sequences which are located at different
co-ordinates on the particle surface. These co-ordinates can be,
for example, polar or tetrahedral in nature, and impart potential
self-assembly properties which allow the nanostructures to form 2
and 3 dimensional photonic and electronic structures (such as the
photonic band gap structures). FIG. 36 (upper) shows a generalized
diagram of a the nanosphere (20 nm diameter) with multiple DNA
sequence identities in polar and equatorial positions. FIG. 36
(lower) also shows some simple structures that could be formed by
hybridizing the nanospheres together.
[0184] FIG. 37 shows the initial steps for producing such
nanostructures. In step (1), a suitably functionalized nanosphere
(with amine groups) is reacted with aldehyde modified
oligonucleotides with sequence identity (A). Identity (A) refers to
a unique sequence of bases in the DNA; for example a 20-mer
oligonucleotide with a 5'-GCACCGATTCGATACCGTAG-3' sequence
(Sequence ID #1). In step 2, the oligo (A) modified nanospheres are
now hybridized to a microlocation surface (with an underlying
electrode) which has a complementary A' sequence
(5'-CTACGGTATCGAATCGGTGC- -3') (Sequence ID #2). The (A') sequence
contains a crosslinker agent (psoralen) and extends into a
secondary sequence with (B) identity (5'-TTCAGGCAATTGATCGTACA-3')
(Sequence ID #3), which was in turn hybridized to a (B) DNA
sequence (5'-TGTACGATCAATTGC CTGAA-3') (Sequence ID #4)covalently
linked to the surface. In step 3 the hybridized nanospheres are now
given a short exposure to UV irradiation which causes the psoralen
moiety within the (A/A') hybridized sequence to covalently
crosslink. The nanospheres are now de-hybridized (passively or
electronically) from the surface. The nanospheres now have a (B)
DNA sequence identity imparted to a polar position on the
structures. FIG. 38 shows the continuation of the processing
scheme. In steps 4 and 5, the (B) DNA sequence identity modified
nanospheres are now "partially hybridized" to a new microlocation
which in turn has been hybridized with a (C-A') sequence, to a
complementary C' sequence which is covalently linked to the
surface. The (C) sequence is different form the (A) and the (B) DNA
sequences. The (B) DNA sequence nanobeads partially hybridize to
the surface via the (A/A') DNA sequences, however they are not
oriented in any particular fashion on the surface. Because the (B)
DNA nanospheres have a non-uniform negative charge distribution on
their surface (due to the extra charge from the (B) DNA, they can
be oriented in an electric field. In step 6, a secondary electrode
is positioned above the lower electrode, and an electric field
strength is applied which is strong enough to orient the
nanospheres, but does not de-hybridize them from the surface. While
FIG. 38 shows the nanospheres in a polar orientation, in terms of
the (B) and (C) sequences; the relative positioning of the
electrodes can produce electric fields which yield other angles for
the relative position of the (B) and (C) DNA sequences. When the
nanospheres are in their correct alignment, they can be completely
hybridized (A'-C/C'), by lowering the temperature, and then exposed
to UV irradiation to crosslink the (A/A') sequences. Upon
de-hybridization, this produces a nanosphere with (B) and (C) DNA
sequences with relative polar (north and south) positions. We
believe that repeating the process two more times can produce
nanospheres with (B), (C), (D), and (E) DNA identities in
polar/equatorial or tetrahedral coordinates.
[0185] Multi-Step and Multiplex Synthesis and Fabrication
Techniques and Devices
[0186] Various techniques and devices can be used to carry out
multi-step and multiplex synthesis and fabrication. FIG. 39 shows a
microelectronic array device with 64 microelectrodes arranged in an
8.times.8 matrix, and four larger control electrodes just outside
the matrix. Electrode structures on the device can range in size
from .about.1 micron to several centimeters or more in large scale
or macroscopic versions of these devices. Permeation layers and/or
template materials may be placed over such devices which would
allow the devices to be used to carry out multi-step and multiplex
synthesis reactions and fabrication steps on substrate materials.
Thus, devices can be used for multi-step and multiplex reactions
and fabrication on "themselves"; as well as manufacturing devices,
which produce the assembled systems on various substrate materials.
We define "multi-step" processes as these which have more than one
synthesis or fabrication step at one or more locations on the
device; and "multiplex" as processes involving the synthesis or
fabrication of different components on different locations on the
device.
[0187] FIG. 40 shows the process by which multi-step transport and
positioning of nanospheres or nanoparticles can be carried out
using such devices. In this sequence of figures, negatively charged
nanostructures (type 1) a re transported a nd concentrated from the
bulk solution onto specific microlocations on the left side of the
array. This is achieved by biasing the microlocations positive,
relative to the control electrodes biased negative. The negatively
charged type 1 nanostructures within the electric field are
transported and concentrated (electrophoretically) at the specific
microlocations. The type 1 nanostructures can be various devices or
structures which have specific DNA sequences which allows them to
hybridize at other specific locations on the device itself or to
other nanostructures which contain complimentary DNA sequences.
[0188] In the next step, type 2 nanostructures a retransported and
concentrated at specific microlocations on the right side of the
device. In the next steps, the type 1 nanostructures are
transported to specific microlocations at the center of the array
which have complimentary DNA attached. The type 1 nanostructures
are transported to specific microlocations at the center of the
array which have complimentary DNA attached. The type 1
nanostructure hybridize and become specifically attached to these
locations. The type 2 nanostructures are now transported to the
same center location, as the type 1 nanostructures. The type 2
nanostructures are now transported to the same center location as
the type 1 nanostructures. The type 2 nanostructures contain
attached DNA sequences which are complimentary to the type 1
nanostructures. The type 2 nanostructures hybridize and become a
bound layer over the type 1 nanostructures.
[0189] This sequence of steps in FIG. 40 is meant to depict only
one of numerous multi-step and multiplex fabrication scenarios
which can be carried out with these devices and self-assembling
nanostructures, submicron and micron sized structures to which
specific DNA sequences are attached. We refer to these processes as
electric field assisted self-assembly of DNA derivatized
structures. By way of example, FIG. 41 shows a sequence of photos
which demonstrate the transport of 200 nanometer sized fluorescent
nanospheres to selected microlocations on an 8.times.8
microelectrode array device. The microlocations are
50.quadrature.m.times.50.quadrature.m in size. The negatively
charged 200 nm fluorescent nanospheres are rapidly transported and
concentrated onto the positively charged microlocations. In other
experimental work, nanospheres have been moved from one location to
other locations on the device; and it is possible to form various
patterns or arrangements of nanostructures on these devices.
[0190] Positioning and Orientation of Large Structures
[0191] One useful application of this invention involves the
attachment and orientation of larger (10-100 micron) sized devices
onto substrate or motherboard materials. This process is shown in
FIG. 42. In this example, a device is selectively derivatized with
four different DNA sequences, and the host board is selectively
derivatized with the four complimentary sequences. The devices are
then allowed to hybridize and attach to the substrate by the
processes which were described in earlier sections on passive and
active electric field methods for hybridization.
[0192] Nanofabrication Within Microelectronic Parameters
[0193] Within the scope of this invention are applications which
involve the nanofabrication of arrangements of nanostructures and
sub-micron devices wtihin parameters of microelectronic,
optoelectronic, and optical components. In these cases,
microelectronic deivces are designed and built by classical
procedures, but contain areas which are designed for self-assembly
of nanostructures and sub-micron cmponents. By way of example, FIG.
43 shows one such device. In this example, a microelectronic device
built in silicon using classical photolithographic techniques, has
a well structure with an underlying micro microelectrode. This
microelectrode is now used to carry out the electric field assisted
self-assembly of various nanostructures and sub-micron components
within the parameter of the microelectronic components. This
technique allows interconnection between the microelectronic
components and the nanoscale components, as well as the creation of
much denser integrated devices including arrangements of multiple
layers (3D fabrication) of components. Thus, this invention is
considered a way to synergize both classical microelectronics
(optoelectronic) fabrication techniques, with self-assemblying
nanofabrication techniques.
[0194] Nanofabrication Within Nanoscale Parameters
[0195] Within the scope of this invention are techniques which
allow the nanofabrication of the matrix of selective binding DNA
sequences to be assembled with a group of nanoscale or sub-micron
positions which have been deposited by atomic force, microscope,
e-beam, or other sub-micron fabrication techniques. FIG. 44 shows
an example of this methodology. In this example, four sub-micron
attachment structures are deposited onto a suitable substrate
material. Two of the structures are of mataerial which can be
selectively activated for subsequent attachment of DNA sequences
(i.e., gold for thiol attachment chemistry). The other two, of a
material which can be selectively activated for another specific
attachment chemistry (i.e., silicon dioxide for silane
aldehyde/amine attachment chemistry). From these positions two
different DNA sequences can be attached. In further steps,
complimentary DNA sequences are hybridized which span the two
different locations forming a square parameter. From proper
position of other DNA sequences can be hybridized to the parameter
DNA, ultimately forming a matrix structure which has selective
hybridization sites within the matrix. From these types of matrix
nanostructures (with selective DNA identities) a variety of two and
three dimensional nanofabrications can be carried out.
[0196] Methods and Apparatus for Optical Writing
[0197] DNA optical storage involves the design and synthesis of
chromophoric DNA polymers which absorb light energy at a single
wavelength and re-emit at predetermined multiple wavelengths. Our
work shows that DNA polymers can be attached in a self-organized
manner to solid surfaces and made into unit cells that have the
designed functionality. We demonstrated that DNA polymers attached
to solid surfaces could exhibit multiple chromophoric responses,
photonic energy transfer, and quenching. FIG. 6 and FIG. 7 show
results related to attachment of fluorescent DNA polymers to
silicon dioxide and aluminum surfaces and UV writing (imaging) into
monolayers of DNA on the surface of these substrates.
[0198] UV Write Mechanism for DNA Optical Storage
[0199] Four different mechanisms exist by which information can be
written into DNA substrate materials: i) spatial UV inactivation of
thymidines within DNA sequences; ii) spatial UV inactivation of
fluorophores and chromophores; iii) spatial UV inactivation or
activation of quencher chromophores; and iv) spatial UV activation
or inactivation of subsequent hybridization by crosslinking (e.g.,
psoralens).
[0200] FIG. 8a and b shows UV write/hybridization results using a
logo mask and a four color write mask. These represent images that
are produced in monolayers of DNA on silicon substrates to which
complementary fluorescent DNA sequences are hybridized.
[0201] UV/psoralen Write Process--Step 1
[0202] Regarding the UV/psoralen write process, FIGS. 9 thru 19,
schematically show the complete process for preparing a "four
identity DNA substrate material".
[0203] This process imparts multiple DNA identities in substrate
materials using psoralen crosslinking agents. DNA intercalated
psoralen compounds when exposed to low-energy UV light (365 nm) are
able to covalently crosslink the DNA strands together. Linking DNA
strands together with psoralen allows creation multiple identities
on substrate surfaces.
[0204] FIG. 9 shows DNA sequences with identity (A) covalently
attached to the Silicon/Aluminum/Silicon Dioxide substrate surface.
The chip surface is first reacted with aminopropyltriethoxysilane
(APS) reagent, which provides amine groups on the substrate surface
for attaching the DNA sequences. The capture DNA sequences (A) are
functionalized in their terminal position with a ribonucleoside
group which is subsequently oxidized to form an amine reactive
dialdehyde group. The DNA (A) sequences can now be covalently
coupled to the amine groups on the APS functionalized substrate
surface. For purposes of illustration the figures show four
individual DNA strands as a way to depict the four potential write
identity quadrants (refereed to as locations in the figures). In
the actual material there are from .about.2.5.times.10.sup.4 to
2.5.times.10.sup.5 DNA strands per quadrant (quadrant size is
preferably about 250 nm square).
[0205] FIG. 10 shows the write identity process is initiated by
hybridizing a (B) identity psoralen modified DNA sequence that is
also partially complementary to the (A) identity capture sequence
existing in all four quadrants (locations). The psoralen molecules
intercalate within the hybridized double-stranded DNA.
[0206] FIG. 11 shows a UV mask is now used to block quadrant 1,
while quadrants 2, 3 and 4 are exposed. The unmasked quadrants (2,
3 & 4) are irradiated with low-energy UV light (365 nm). The UV
exposure causes the intercalated psoralen molecules within the
hybridized double-stranded DNA to covalently crosslink the
strands.
[0207] FIG. 12 shows the entire surface is now subjected to a
dehybridization process. The non-crosslinked (B) identity DNA
sequence in quadrant 1 is removed, leaving the (A) identity DNA
sequence in that position. Quadrants 2, 3 & 4 now have the (B)
identity DNA sequence in their positions.
[0208] FIG. 13 shows the process is now repeated with a (C)
identity DNA sequence, containing the partial (B) identity DNA
complement, being hybridized to the (B) sequence in quadrants 2, 3
and 4.
[0209] FIGS. 14 thru 18 depict essentially the repetition of the
processes shown in FIGS. 9 thru 13. When completed, the final
material contains four separate DNA identity sequences (A, B, C,
& D) each located in a separate quadrant.
[0210] FIG. 19 shows, at this point, where one can check the
specificity of the four DNA sequences (A, B, C, & D) by
hybridizing the four fluorescently labeled complementary sequences
to the surface. Each quadrant should now produce its specific
fluorescent color.
[0211] UV/psoralen Write Process--Step 2
[0212] The actual information UV write process (to the four DNA
identity substrate) is carried out by another masking and UV
exposure procedure (see FIGS. 20, 21, and 22). In this case, a
higher energy UV irradiation (254 nm) is used to render the DNA in
the UV exposed regions non-hybridizable. When DNA is exposed to
this higher energy UV light, the thymidine bases within the DNA
sequence dimerize and prevent any further hybridization from
occurring. This procedure can thus be used to inactivate the
individual quadrants or "turn them off". When the fluorescently
labeled complementary DNA sequences are hybridized to the material,
only the quadrants with hybridizable complementary DNA sequences
will have the appropriate fluorescent color. This is the mechanism
by which data can be selectively written into DNA.
[0213] FIGS. 20 & 21 show turning "On" the B and D identities,
and turning "Off" the A and C identities. Before the UV write
process is started, the specific A, B, C, & D sequences in all
four quadrants 1, 2, 3, & 4 are hybridizable. The write process
is initiated by masking quadrants 2 and 4, and exposing the surface
to the high-energy (254 nm) UV irradiation. Quadrants 1 and 3 are
now effectively inactivated or made unhybridizable by UV exposure,
while the DNA sequences in 2 & 4 remain hybridizable.
[0214] FIG. 22 shows how the material can now be hybridized with
the fluorescent DNA complements to all four DNA identities,
however, only the fluorescent DNA complements to the B and D
identities will effectively hybridize and produce the final
fluorescent colors. The UV write process being completed, the
material now has two distinct fluorescent colors in the B and D
quadrants, and no fluorescent colors in the A and C quadrants.
[0215] Experimental Demonstration of Two Color DNA Write
Process
[0216] We have demonstrated two color write using the psoralen/UV
process. The series of process and write steps are described below
in the text. FIGS. 23A &B, 24 A&B, and 25 A&B show the
actual photographs of the substrate and fluorescent write
materials. FIGS. 27A, B &C, and 28 A, B&C, provide further
schematic descriptions of the process.
[0217] Step 1: A control chip surface (Silicon
Dioxide/Aluminum/Silicon) was treated with
Aminopropyltriethoxysilane (APS). FIG. 23-A shows the chip surface
appears basically black, because of the relatively low level of
background fluorescence. FIG. 27-A is a schematic representation of
the material at this point of the process. All photographs were
taken using the Jenalumar Epi-fluorescent microscope/Hammamatsu
Intensified CCD Camera/Argus Ten Imaging system.
[0218] Step 2: A second control chip surface (APS reacted) was then
reacted with the DNA (A) identity capture sequence that contains
the proper base composition for subsequent psoralen crosslinking.
The DNA (A) sequence has a ribo group on the 3' end that is
oxidized to a dialdehyde, this reacts with the amine groups on the
surface to covalently attach the DNA. FIG. 23-B shows a photograph
of the substrate surface with the DNA (A) present, but without any
fluorescent complementary DNA present. The chip surface still
appears black, because of the relatively low level of background
fluorescence. FIG. 27-B is a schematic representation of the
material at this point of the process.
[0219] Step 3: A third control chip surface which has been APS
reacted and has the DNA (A) capture sequence attached, is
hybridized with a BODIPY Texas Red fluorescently labeled
complementary sequence. FIG. 24-A now shows the entire chip surface
producing intense red fluorescence. FIG. 27-C is a schematic
representation of the material at this point of the process.
[0220] Step 4: A fourth chip is treated with APS and (A) identity
DNA capture sequence is then bound to the surface as in Step 2.
[0221] Step 5: The complementary (B) identity sequence, with a
psoralen molecule attached, is then hybridized to the (A) identity
sequence over the entire surface.
[0222] Step 6: One half of the chip surface is masked, while the
other half is exposed to low-energy (365 nm) UV light. This causes
the covalent crosslinking of the (A) identity DNA sequence with the
(B) identity DNA sequence.
[0223] Step 7: The surface is then treated with a 0.1 normal Sodium
Hydroxide solution to remove (dehybridize) the non-crosslinked DNA
from the masked side of the chip. At this point one half of the
chip is covered with covalently linked (B) identity DNA sequence,
and the half contains the original (A) identity DNA sequence.
[0224] Step 8: A complementary (A) identity DNA sequence labeled
with BODIPY Texas Red fluorescent dye (excitation maximum 595 nm
and emission maximum 626 nm) is now hybridized to the chip. The
complementary fluorescent (A) identity DNA sequence hybridizes only
to the half of the chip surface containing the (A) identity capture
sequence (FIG. 24-B). FIG. 28-A is a schematic representation of
the material at this point of the process. Steps 4 thru 7 are
repeated on a fifth chip surface.
[0225] Step 9: A BODIPY Orange fluorescent dye (excitation maximum
558 nm and emission maximum 568 nm) labeled sequence complementary
only to the (B) identity sequence is then hybridized across the
whole chip. This DNA sequence hybridizes only to the half of the
chip containing the (B) identity (FIG. 25-A). FIG. 28-B is a
schematic representation of the material at this point of the
process.
[0226] Step 10: A sequence complementary only to the (A) identity
capture sequence, labeled with BODIPY Texas Red fluorescent dye is
hybridized to the fifth chip. Again this fluorescently labeled DNA
attaches only to the half of the chip containing the (A) identity.
The chip now contains both identities with their corresponding
colors (FIG. 25-B). FIG. 28-C is a schematic representation of the
material at this point of the process. With the results showing
exclusive hybridization of two distinct sequences to two separate
parts of a chip surface (FIGS. 24-B, 25-A & 25-B), we are
reasonably confident that the above protocol is indeed capable of
producing multiple identities on silicon substrate surfaces.
[0227] Experimental Demonstration of 160 nm Nanosphere Binding to
Substrate
[0228] FIGS. 26A and 26B show results on attaching 160 nm DNA
Derivitized fluorescent nanospheres to a DNA Derivitized silicon
dioxide surface. The nanospheres are bound to the image sections
with the active DNA, as opposed to the DNA in-activated sections.
The binding is believed to be due to electrostatic as well as to
hybridization interactions.
[0229] Low Density Optical Memory Applications
[0230] A number of important applications of DNA based optical data
storage and memory are possible in areas regarding incorporation
into documents, currency, labels, and other items. The use of
fluorescent energy transfer and chromophoric DNA based mechanism
for these "low density" application would have advantages over bar
codes and other methods in use becuase of the extreme difficulty in
attempting to counterfeit such information or coding.
[0231] A Photo-Electronic Optical Memory Write Systems and
Devices
[0232] DNA polymers may be used for many photonic and electronic
applications. One of the main applications using DNA polymers are
for high density optical data storage media. In this application,
chromophoric DNA polymers absorb light energy at a single
wavelength and re-emit at predetermined multiple wavelengths. (See
FIG. 45). In one aspect, these inventions relate to a method called
photo-electronic write process. This process involve using spatial
light addressing to a photoactive substrate material which creates
microscopic electric fields, which then affect the selective
transport and attachment of charged chromophoric (color) DNA's to
these selected locations.
[0233] Principles of Operation
[0234] The basic principle involved in the photo/electronic write
process is show in FIGS. 46.a and 46.b. The proposed write
substrate would be a photo/electronic activated matrix material
(e.g., a photoconductive film) onto which DNA polymer sequences
would be attached. Each of these DNA sequences would have multiple
identities. For the sake of illustration, FIG. 46.a shows three
photoactivated sites, which contain DNA sequences with three
identities (A, B, & C). A solution containing chromophoric DNA
with complementary identity (A') would be exposed to the substrate
material, and a counter electrode would be positioned over the
solution and lower substrate material. The specific microlocations
on the substrate material can now be activated by spatial light
addressing which would cause a charge to develop in the material at
that location (see FIG. 46.b). The production of a charge produces
an electric field in the solution which causes the attraction of
oppositely charged molecules to the location, or will repel
molecules of the same charge identity. Natural DNA would contain a
net negative charge, and will migrate to a positively charged
location. Synthetic DNA's can be made with net negative charge, net
positive charge, or in a neutral state. FIG. 46.b shows the light
activation of the center microlocation 2, with chromophoric DNA
(A') migrating to this location and then binding (hybridizing) to
the DNA (A) identity sequence position. When the electric field
strength is high enough, the transport and concentration of the DNA
chromophore units is extremely rapid; occurring in 1 to 2
seconds.
[0235] The process for producing multiple colors at a specific
microlocations is shown in FIGS. 46.c through 46.f. FIG. 46.c shows
a group of six microlocations, each of which contains a DNA polymer
with A, B, and C sequence identities (only one capture strand is
shown in these figures). Spatial light addressing of positions 1,
3, and 5 is carried out. Chromophoric DNA A' sequences (red) are
transported, concentrated, and hybridized selectively to these
locations. FIG. 46.d shows the process repeated for the next
chromophoric DNA B' sequences (green). Spatial light addressing of
positions 1, 3, and 4 are now carried out. Chromophoric DNA B'
sequences are transported, concentrated, and hybridized selectively
to these locations. FIG. 46.e shows the process repeated for the
next chromophoric DNA C' sequences (blue). Spatial light addressing
of positions 1, 3, 5 and 6, are now carried out. Chromophoric DNA
C' sequences are transported, concentrated, and hybridized
selectively to these locations. The write process being complete,
FIG. 46.f shows the final optical material which now has
chromophore DNA A'/B'/C' (red/green/blue) at microlocations 1 and
3, chromophoric DNA A'/C' (red/blue) at microlocation 5,
chromophoric DNA B' (green) at microlocation 4, chromophoric DNA C'
(blue) at microlocation 6, and no chromophoric DNA (no color) at
microlocation 2.
[0236] In addition to the spatial light activation of
photoconductive materials, other alternatives exist. For example,
electrode array devices may be switched by spatial light
addressing. In yet another example, electrode arrays may be
switched by electronics.
[0237] Although the foregoing invention has been described in some
detail by way of illustration and example for purposes of clarity
and understanding, it may 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.
Sequence CWU 1
1
4 1 20 DNA Artificial Modified oligonucleotide 1 gcaccgattc
gataccgtag 20 2 20 DNA Artificial Modified oligonucleotide 2
ctacggtatc gaatcggtgc 20 3 20 DNA Artificial Modified
oligonucleotide 3 ttcaggcaat tgatcgtaca 20 4 20 DNA Artificial
Modified oligonucleotide 4 tgtacgatca attgcctgaa 20
* * * * *