U.S. patent application number 15/047267 was filed with the patent office on 2016-09-29 for bent nanowires and related probing of species.
The applicant listed for this patent is President and Fellows of Harvard College. Invention is credited to Itzhaq Cohen-Karni, Xiaojie Duan, Thomas J. Kempa, Charles M. Lieber, Quan Qing, Bozhi Tian, Ping Xie.
Application Number | 20160282303 15/047267 |
Document ID | / |
Family ID | 43084250 |
Filed Date | 2016-09-29 |
United States Patent
Application |
20160282303 |
Kind Code |
A1 |
Lieber; Charles M. ; et
al. |
September 29, 2016 |
BENT NANOWIRES AND RELATED PROBING OF SPECIES
Abstract
The present invention generally relates to nanoscale devices and
methods, including bent nanowires and other bent nanoscale objects,
and in particular, the ability to probe cells with nanoscale
objects. In some aspects, nanoscale objects, including nanowires,
are provided that facilitate cell probing, e.g. nanowires that are
surface modified such that cells can fuse with the nanowires.
Devices including nanoscale objects are provided that allow small
or large scale (e.g., multiplexed) probing of cells, and related
methods of making such nanoscale objects and devices, and methods
of investigating cells, are provided by certain embodiments of the
invention. In a related set of embodiments, the present invention
is generally related to bent nanowires and other bent nanoscale
objects. For instance, in one aspect, the present invention is
generally related to a semiconductor nanoscale wire having at least
one kink. The semiconductor nanoscale wire may be formed out of any
suitable semiconductor, e.g., Si, CdS, Ge, or the like. In some
embodiments, a kink in the semiconductor nanoscale wire may be at
an angle of about 120.degree. or a multiple thereof. Yet other
aspects of the invention are generally directed to methods of using
such nanoscale wires, kits involving such nanoscale wires, devices
involving such nanoscale wires, or the like.
Inventors: |
Lieber; Charles M.;
(Lexington, MA) ; Tian; Bozhi; (Chicago, IL)
; Xie; Ping; (Needham, MA) ; Kempa; Thomas J.;
(Somerville, MA) ; Cohen-Karni; Itzhaq;
(Cambridge, MA) ; Qing; Quan; (Somerville, MA)
; Duan; Xiaojie; (Somerville, MA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
President and Fellows of Harvard College |
Cambridge |
MA |
US |
|
|
Family ID: |
43084250 |
Appl. No.: |
15/047267 |
Filed: |
February 18, 2016 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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13497852 |
Jul 2, 2012 |
9297796 |
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PCT/US10/50199 |
Sep 24, 2010 |
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15047267 |
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61326108 |
Apr 20, 2010 |
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61245641 |
Sep 24, 2009 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
H01L 29/0665 20130101;
H01L 51/0048 20130101; B82Y 15/00 20130101; G01N 27/4146 20130101;
G01N 33/48728 20130101; B82Y 10/00 20130101; H01L 29/045 20130101;
H01L 29/0669 20130101; H01L 21/02603 20130101 |
International
Class: |
G01N 27/414 20060101
G01N027/414; H01L 51/00 20060101 H01L051/00; H01L 29/06 20060101
H01L029/06; H01L 21/02 20060101 H01L021/02 |
Goverment Interests
GOVERNMENT FUNDING
[0002] Research leading to various aspects of the present invention
were sponsored, at least in part, under Grant No. OD003900 awarded
by the National Institutes of Health and under Grant No. 67161
awarded by the MITRE Corporation. The U.S. Government has certain
rights in the invention.
Claims
1-44. (canceled)
45. A method, comprising: penetrating a membrane of a cell with a
semiconductor nanoscale object; and electrically communicating with
the cell.
46. The method of claim 45, further comprising determining an
electrical potential inside the cell.
47. The method of claim 45, wherein electrically communicating with
the cell comprises determining an electric field.
48. The method of claim 45, wherein electrically communicating with
the cell comprises electrically communicating with the cell using a
field effect.
49. The method of claim 45, wherein the membrane is a cell
membrane.
50. The method of claim 45, wherein the membrane is an inner
membrane.
51. The method of claim 45, wherein the semiconductor nanoscale
object is bent.
52. The method of claim 45, wherein the semiconductor nanoscale
object has at least one kink.
53. The method of claim 45, wherein the semiconductor nanoscale
object is a wire.
54. The method of claim 45, further comprising inducing an action
potential in the cell.
55. The method of claim 45, wherein the cell is a neuronal
cell.
56. The method of claim 45, wherein the cell is a
cardiomyocyte.
57. The method of claim 45, further comprising electrically
communicating with the cell at a plurality of regions in the
cell.
58. The method of claim 45, wherein the nanoscale object is a
semiconductor nanowire.
59. The method of claim 45, wherein the nanoscale object is a
carbon nanotube.
60-127. (canceled)
Description
RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. Provisional
Patent Application Ser. No. 61/245,641, filed Sep. 24, 2009,
entitled "Bent Nanowires," by Tian, et al.; and the benefit of U.S.
Provisional Patent Application Ser. No. 61/326,108, filed Apr. 20,
2010, entitled "Bent Nanowires and Related Probing of Species," by
Tian, et al. Each of these is incorporated herein by reference.
FIELD OF INVENTION
[0003] The present invention generally relates to nanoscale devices
and methods, including bent nanowires and other bent nanoscale
objects, and in particular, the ability to probe cells with
nanoscale objects.
BACKGROUND
[0004] Interest in nanotechnology, in particular
sub-microelectronic technologies such as semiconductor quantum dots
and nanowires, has been motivated by the challenges of chemistry
and physics at the nanoscale, and by the prospect of utilizing
these structures in electronic and related devices. While
nanoscopic articles might be well-suited for transport of charge
carriers and excitons (e.g. electrons, electron pairs, etc.) and
thus may be useful as building blocks in nanoscale electronics
applications, other than standard small-scale lithographic
techniques, nanoelectronics is not a well-developed field. Thus
there is a need in the art for new and improved articles and
techniques involving nanoelectronics.
SUMMARY OF THE INVENTION
[0005] The present invention generally relates to nanoscale devices
and methods, including bent nanowires and other bent nanoscale
objects, and in particular, the ability to probe cells with
nanoscale objects. The subject matter of the present invention
involves, in some cases, interrelated products, alternative
solutions to a particular problem, and/or a plurality of different
uses of one or more systems and/or articles.
[0006] According to one aspect, the present invention is generally
directed to an article. In one set of embodiments, the article
includes a semiconductor nanoscale wire having at least one kink.
In some cases, the semiconductor nanoscale wire comprises or
consists essentially of a <112> crystallographic orientation
and/or a <1120> crystallographic orientation. In certain
instances, the semiconductor nanoscale wire consists essentially of
one crystallographic orientation.
[0007] In accordance with one set of embodiments, the article is
directed to a wire having at least one kink. In some embodiments,
the wire may consist essentially of a single semiconductor
material, for example, CdS, Ge, or Si.
[0008] The invention, in another aspect, is directed to a method of
growing a semiconductor nanoscale wire. In one set of embodiments,
the method includes acts of growing a semiconductor nanoscale wire
from a catalyst particle in a first direction by exposing the
catalyst particle to a first gaseous reactant, isolating the
catalyst particle from the first gaseous reactant, and growing the
semiconductor nanoscale wire from the catalyst particle in a second
direction by exposing the catalyst particle to a second gaseous
reactant, where the second direction is substantially different
from the first direction.
[0009] In one aspect, an article is provided. The article comprises
a nanoscale wire having at least one kink, wherein at least a
portion of a surface of the nanoscale wire is amphiphilic.
[0010] In another aspect, an article is provided. The article
comprises a nanoscale wire having at least one kink, wherein at
least a portion of a surface of the nanoscale wire is capable of
fusing with a lipid bilayer.
[0011] In still another aspect, an article is provided. The article
comprises a nanoscale wire having at least one kink, wherein at
least a portion of the nanoscale wire is capable of penetrating a
lipid bilayer using chemical interactions.
[0012] In yet another aspect, a method is provided. The method
comprises contacting a cell membrane with a nanoscale object. The
method further comprises allowing the cell membrane to fuse with
the nanoscale object.
[0013] In still another aspect, a method is provided. The method
comprises contacting a cell membrane with a nanoscale object. The
method further comprises allowing the nanoscale object to penetrate
the cell membrane using chemical interactions.
[0014] In yet another aspect, a method is provided. The method
comprises penetrating a membrane of a cell with a semiconductor
nanoscale object. The method further comprises electrically
communicating with the cell.
[0015] In still another aspect, a method is provided. The method
comprises providing a cell. The method further comprises
determining an electrical potential inside the cell using field
effect.
[0016] In yet another aspect, a device is provided. The device
comprises a substrate having a plurality of nanoscale objects
disposed thereon, wherein at least a portion of a surface of each
of the plurality of nanoscale objects is amphiphilic.
[0017] In still another aspect, a device is provided. The device
comprises a substrate having a plurality of nanoscale objects
disposed thereon, wherein at least a portion of a surface of each
of the plurality of nanoscale objects is capable of fusing with a
lipid bilayer.
[0018] In yet another aspect, a device is provided. The device
comprises a substrate having a plurality of nanoscale objects
disposed thereon, wherein each of the plurality of nanoscale
objects is capable of penetrating a lipid bilayer using chemical
interactions.
[0019] In still another aspect, a method is provided. The method
comprises contacting a cell membrane with a device, the device
comprising a substrate having a plurality of nanoscale objects
disposed thereon. The method further comprises allowing at least
some of the plurality of nanoscale objects to fuse with the cell
membrane.
[0020] In yet another aspect, a method is provided. The method
comprises contacting a cell membrane with a device, the device
comprising a substrate having a plurality of nanoscale objects
disposed thereon, and penetrating the cell membrane with at least
some of the plurality of nanoscale objects. The method further
comprises determining an electrical potential inside the cell using
field effect.
[0021] In still another aspect, a method is provided. The method
comprises contacting a cell with a drug candidate. The method
further comprises measuring an electrical potential inside the cell
using field effect.
[0022] In another aspect, the present invention is directed to a
method of making one or more of the embodiments described herein,
for example, bent nanowires and other bent nanoscale objects. In
another aspect, the present invention is directed to a method of
using one or more of the embodiments described herein, for example,
bent nanowires and other bent nanoscale objects.
[0023] Other advantages and novel features of the present invention
will become apparent from the following detailed description of
various non-limiting embodiments of the invention when considered
in conjunction with the accompanying figures. In cases where the
present specification and a document incorporated by reference
include conflicting and/or inconsistent disclosure, the present
specification shall control. If two or more documents incorporated
by reference include conflicting and/or inconsistent disclosure
with respect to each other, then the document having the later
effective date shall control.
BRIEF DESCRIPTION OF THE DRAWINGS
[0024] Non-limiting embodiments of the present invention will be
described by way of example with reference to the accompanying
figures, which are schematic and are not intended to be drawn to
scale. In the figures, each identical or nearly identical component
illustrated is typically represented by a single numeral. For
purposes of clarity, not every component is labeled in every
figure, nor is every component of each embodiment of the invention
shown where illustration is not necessary to allow those of
ordinary skill in the art to understand the invention. In the
figures:
[0025] FIGS. 1A-1E illustrate the design and synthesis of nanoscale
wires containing kinks, according to one set of embodiments;
[0026] FIGS. 2A-2F illustrate various nanoscale wires containing
kinks, in certain embodiments of the invention;
[0027] FIGS. 3A-3F illustrate various nanoscale wires containing
kinks and growth thereof, in another set of embodiments;
[0028] FIGS. 4A-4D illustrate various semiconductor nanoscale
wires, in other embodiments of the invention;
[0029] FIGS. 5A-5E illustrate various nanoelectronic devices
containing nanoscale wires, in one set of embodiments;
[0030] FIGS. 6A-6B illustrate kinked semiconductor nanowire
superstructures, in another set of embodiments;
[0031] FIG. 7 illustrates growth orientation statistics for kinked
nanoscale wires, according to one embodiment of the invention;
[0032] FIG. 8 illustrates a kinked nanoscale, wire, in another
embodiment of the invention;
[0033] FIG. 9A shows schematics of bent nanoscale objects,
according to an embodiment;
[0034] FIG. 9B shows an SEM image of a bent nanoscale object,
according to an embodiment;
[0035] FIG. 9C shows a cis/(cis+trans) vs. L plot, according to an
embodiment;
[0036] FIG. 9D shows a TEM image of a bent nanoscale object,
according to an embodiment;
[0037] FIG. 9E shows an SEM image of a bent nanoscale object,
according to an embodiment;
[0038] FIG. 9F shows an SEM image of a bent nanoscale object,
according to an embodiment;
[0039] FIG. 9G shows an SEM image of a bent nanoscale object,
according to an embodiment;
[0040] FIG. 10A shows schematics of device fabrication, according
to an embodiment;
[0041] FIG. 10B shows an SEM image of a bent nanoscale object,
according to an embodiment;
[0042] FIG. 10C shows a plot of device conductance and sensitivity
under external bending and shows an experiment schematic of
external bending (inset), according to an embodiment;
[0043] FIG. 10D shows a plot demonstrating nanoscale pH sensor
properties and shows an experiment schematic, according to an
embodiment;
[0044] FIG. 11A shows schematics of nanowire entrance into a cell,
according to an embodiment;
[0045] FIG. 11B shows a false colored fluorescence image of a lipid
coated nanowire probe, according to an embodiment;
[0046] FIG. 11C shows differential interference contrast (DIC)
microscopy images (upper panel) and shows a plot of electrical
recording (lower panel) of an HL-1 cell interacting with a
phospholipid coated 60.degree. kinked nanowire probe, according to
an embodiment;
[0047] FIG. 11D shows a plot of electrical recording with a
60.degree. kinked nanowire probe without phospholipids surface
modification (refers to FIG. 11C, top panel), according to an
embodiment;
[0048] FIG. 12A shows schematics of cellular recording from
cardiomyocyte monolayer on PDMS (left panel) and zoomed-in extra-
and intracellular nanowire/cell interfaces (right panels),
according to an embodiment;
[0049] FIG. 12B shows DIC images of cells and a device used in
extra- and intracellular measurements, according to an
embodiment;
[0050] FIG. 12C shows plots of electrical recordings from beating
cardiomyocytes, according to an embodiment;
[0051] FIG. 12D shows magnified portions of FIG. 12C referring to
the dashed square regions in FIG. 12C, according to an
embodiment;
[0052] FIGS. 13A-13D show TEM images of nanoscale objects,
according to an embodiment;
[0053] FIG. 14B shows an atomic force micrograph (left panel) and
scanning gate micrographs (middle panel and right panel), according
to an embodiment;
[0054] FIGS. 15A-15B shows a schematic of fabrication steps and
shows a plot of dependence of the tip height and angle versus the
length of relieved metal, according to an embodiment;
[0055] FIG. 16A shows a plot of conductance vs. water-gate voltage
measurements for a typical free-standing nanowire probe device,
according to an embodiment; and
[0056] FIG. 16B shows a plot of calibrated nanowire surface
potential change vs. solution pH, according to an embodiment.
DETAILED DESCRIPTION
[0057] The present invention generally relates to nanoscale devices
and methods, including bent nanowires and other bent nanoscale
objects, and in particular, the ability to probe cells with
nanoscale objects. In some aspects, nanoscale objects, including
nanowires, are provided that facilitate cell probing, e.g.
nanowires that are surface modified such that cells can fuse with
the nanowires. Devices including nanoscale objects are provided
that allow small or large scale (e.g., multiplexed) probing of
cells, and related methods of making such nanoscale objects and
devices, and methods of investigating cells, are provided by
certain embodiments of the invention. In a related set of
embodiments, the present invention is generally related to bent
nanowires and other bent nanoscale objects. For instance, in one
aspect, the present invention is generally related to a
semiconductor nanoscale wire having at least one kink. The
semiconductor nanoscale wire may be formed out of any suitable
semiconductor, e.g., Si, CdS, Ge, or the like. In some embodiments,
a kink in the semiconductor nanoscale wire may be at an angle of
about 120.degree. or a multiple thereof. Yet other aspects of the
invention are generally directed to methods of using such nanoscale
wires, kits involving such nanoscale wires, devices involving such
nanoscale wires, or the like.
[0058] The present invention generally relates to bent nanowires
and other bent nanoscale objects according to certain embodiments.
For instance, some embodiments of the invention are directed to a
semiconductor nanoscale wire having at least one kink. For example,
the wire may have 2, 3, 4, 5, etc. kinks. The semiconductor
nanoscale wire may be formed out of any suitable semiconductor,
e.g., Si, CdS, Ge, or the like. In some cases, the semiconductor
nanoscale wire consists essentially of a single crystallographic
orientation, for example, a <112> crystallographic
orientation or a <1120> crystallographic orientation. In some
embodiments, a kink in the semiconductor nanoscale wire may be at
an angle of about 120.degree. or a multiple thereof. The kinks may
be intentionally positioned along the nanoscale wire in some cases,
e.g., using methods such as those described herein. For example, in
one aspect, a nanoscale wire may be grown from a catalyst particle
by exposing the catalyst particle to various gaseous reactants to
cause the formation of one or more kinks within the nanoscale
wire.
[0059] As mentioned, in some embodiments, the present invention
generally relates to nanoscale devices and methods and, in one
important aspect, the ability to probe cells with nanoscale
objects. Nanoscale objects, including nanowires, are provided that
facilitate cell probing, e.g. nanowires that are surface modified
such that cells can fuse with the nanowires. Devices including
nanoscale objects are provided that allow small or large scale
(e.g., multiplexed) probing of cells, and related methods of making
such nanoscale objects and devices, and methods of investigating
cells, are provided by certain embodiments of the invention.
[0060] The following applications are incorporated herein by
reference in their entireties: U.S. Provisional Patent Application
Ser. No. 61/245,641, filed Sep. 24, 2009, entitled "Bent
Nanowires," by Tian, et al.; and U.S. Provisional Patent
Application Ser. No. 61/326,108, filed Apr. 20, 2010, entitled
"Bent Nanowires and Related Probing of Species," by Tian, et
al.
[0061] In one aspect, a nanoscale object that can integrate with a
lipid bilayer is described. In some embodiments, at least a portion
of a surface of the nanoscale object may be modified such that it
is capable of fusing with a lipid bilayer. For example, the
nanoscale object may include a coating that can interact with a
lipid bilayer. In some embodiments, the nanoscale object may be
formed out of any suitable semiconductor, e.g., Si, CdS, Ge, or the
like. In some cases, a nanowire may have at least one kink. For
example, the wire may have 2, 3, 4, 5, etc. kinks. In some
embodiments, the nanoscale object may be used to communicate
electrically with a cell. For example, the nanoscale object may be
used to determine the electrical potential inside a cell. In
another aspect, a device including a plurality of nanoscale objects
disposed on a substrate is provided. In some embodiments, the
device may be used to communicate electrically with a plurality of
cells. In some embodiments, the device may be used to communicate
electrically with a plurality of (i.e., multiple) regions of a
cell. In some cases, electrical communication with a plurality of
regions of a cell may occur essentially simultaneously. Yet other
aspects of the invention are generally directed to methods of using
such nanoscale wires, kits involving such nanoscale wires, devices
involving such nanoscale wires, or the like.
[0062] In another aspect, a nanoscale device may be constructed
that includes a nanoscale wire and/or other nanoscale object. In
some embodiments, the nanoscale object may be a semiconductor.
Nanoscale objects may, in some embodiments, be bent, i.e., they do
not describe a straight line. In some embodiments, the nanoscale
object may have at least one kink. As discussed below, there may be
any number of kinks present within the nanoscale object, depending
on the embodiment, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more
kinks. In a semiconductor nanoscale object, the semiconductor may
be formed from one, or more than one, semiconductor material, for
example, silicon, germanium, cadmium sulfide (CdS), or the like.
Further non-limiting examples of semiconductor materials
potentially suitable for use in semiconductor nanoscale objects are
discussed in detail below. In some embodiments, the nanoscale
object may be a nanoscale wire.
[0063] In some embodiments, a nanoscale object may be
surface-functionalized. In some cases, only a portion of the
surface may be functionalized. Surface-functionalization may be
achieved, in some embodiments, by coating at least a portion of the
nanoscale object (e.g., with a shell). In another embodiment, at
least a portion of the nanoscale object may be functionalized by
performing a chemical reaction on the surface of the nanoscale
object.
[0064] In some cases, surface-functionalization comprises attaching
a functional moiety to the surface of the nano scale object. In
some embodiments, a functional moiety may be attached directly to
the surface of the nanoscale object (i.e., through a chemical
bond). In another embodiment, the functional moiety may be attached
to a coating on a nanoscale object.
[0065] The functional moieties may include simple functional
groups, for example, but not limited to, --OH, --CHO, --COOH,
--SO.sub.3H, --CN, --NH.sub.2, --SH, --COSH, COOR, or a halide;
biomolecular entities including, but not limited to, amino acids,
proteins, sugars, DNA, antibodies, antigens, and enzymes; grafted
polymer chains with chain length less than the diameter of the
nanoscale wire core, including, but not limited to, polyamide,
polyester, polyimide, polyacrylic; a thin coating (e.g., shell),
covering the surface of the nanoscale object core, including, but
not limited to, the following groups of materials: metals,
semiconductors, and insulators, which may be a metallic element, an
oxide, an sulfide, a nitride, a selenide, a polymer and a polymer
gel. In another embodiment, the invention provides a nanoscale
object and a reaction entity with which the analyte interacts,
positioned in relation to the nanoscale object such that the
analyte can be determined by determining a change in a
characteristic of the nanoscale object.
[0066] In some embodiments, a nanoscale object may be at least
partially coated (e.g., with a shell). In some embodiments, the
coating may comprise an amphiphilic material. Non-limiting examples
of amphiphilic materials include phospholipids, such as
phosphatidate, phosphatidylethanolamine, phosphatidylcholine,
phosphatidylserine, phosphatidylinositol, phosphatidylinositol
phosphate, phosphatidylinositol bisphosphate, and
phosphatidylinositol triphosphate, surfactants, polymers, proteins,
and polysaccharides.
[0067] In some cases, surface-functionalized nanoscale objects
(e.g. nanoscale objects having shells comprising functional
moieties) may be coupled to a substrate surface with functional
cross-linkers, such as homobifunctional cross-linkers, comprising
homobifunctional NHS esters, homobifunctional imidoesters,
homobifunctional sulfhydryl-reactive linkers, difluorobenzene
derivatives, homobifunctional photoactive linkers, homobifunctional
aldehyde, bis-epoxides, homobifunctional hydarzide etc.;
heterobifuntional cross-linkers; or trifuntional cross-linkers. In
another embodiment, a region may include amorphous oxide, which may
allow other molecules to be attached to the surface of the region.
This may facilitate attachment or modification, in certain
instances.
[0068] Nanoscale objects may be surface-functionalized using any
suitable method. In some embodiments, a nanoscale object may be
cleaned using plasma prior to functionalization. A nanoscale object
may be surface-functionalized, in some embodiments, by contacting
the nanoscale object with vesicles. For example, the nanoscale
object may be placed into a suspension of vesicles, where the
vesicles comprise an amphiphilic material such as a phospholipid.
Without wishing to be bound by any theory, it is believed that
contacting the nanoscale object with vesicles, where the vesicles
comprise an amphiphilic material, results in spontaneous formation
of a coating of the amphiphilic material on the nanoscale object.
In some embodiments, the suspension of vesicles may be formed as
follows. An amphiphilic material (e.g., a phospholipid) may be
dissolved in a suitable solvent. For example, the amphiphilic
material may be dissolved in an organic solvent, such as
chloroform. In some cases, the solution of amphiphilic material may
be evaporated, for example, under flow of gas (e.g., nitrogen or
argon). In some embodiments, the amphiphilic material may be
hydrated by adding water or an aqueous solution to the amphiphilic
material. In some cases, the aqueous mixture of amphiphilic
material may be frozen and thawed one or more times. The aqueous
mixture of amphiphilic material may, in some embodiments, be
sonicated.
[0069] In one aspect, nanoscale objects such as those described
herein may be used as biological probes, for example, for the
detection of cells, proteins, nucleic acids, carbohydrates,
saccharides, lipids, antibodies, or other biological entities. In
some embodiments, the nanoscale objects may be used in tissue
samples, such as brain slices or cardiac tissues. As an example, in
one set of embodiments, nanoscale objects may be attached to
electrodes using techniques such as those described herein, e.g.,
to form a transistor, such as a field effect transistor. In some
embodiments, such transistors may be used as probes, e.g., as
probes for biological systems. For instance, the transistors may be
used to probe cells or tissues, for example, cardiomyocytes or
neurons, and/or in contact with three-dimensional tissue sections.
For instance, using such nanoscale objects as probes, the nanoscale
objects may be used to determine electrical properties of cells or
tissues, including in regions below the surface layer of the
tissue, due to the shape of the nanoscale objects.
[0070] In some embodiments, a nanoscale object may be capable of
interacting (e.g., chemically) with a lipid bilayer. For example, a
nanoscale object may contact the lipid bilayer and fuse with the
lipid bilayer. As used herein, "fuse" means that the nanoscale
object integrates into the lipid bilayer such that the lipid
bilayer is continuous around one or more portions of the nanoscale
object. In some embodiments, the lipid bilayer may rearrange around
at least a portion of the nanoscale object. In some embodiments, at
least two lipid bilayers may fuse with a nanoscale object. For
example, a nanoscale object may fuse with the cell membrane of a
cell and with at least one inner membrane of a cell (e.g., a
membrane of an organelle).
[0071] In some embodiments, integration of a nanoscale object into
a lipid bilayer is achieved with mechanical force. For example, a
nanoscale object may penetrate a lipid bilayer by being pushed
through the lipid bilayer. One of ordinary skill in the art would
recognize that such a method requires an input of energy (e.g.,
applying a force to an object such that the object displaces along
a vector). However, in some embodiments, substantially less energy
may be required for a surface-functionalized nanoscale object to
penetrate a lipid bilayer, i.e., favorable chemical interactions
may occur between the nanoscale object and the lipid bilayer. In
some embodiments, a surface-functionalized nanoscale object may
spontaneously penetrate the lipid bilayer. In some embodiments, the
nanoscale object and/or the entity comprising the lipid bilayer may
be manipulated such that the nanoscale object and the lipid bilayer
are brought into contact. For example, a cell may be manipulated
using a micropipette and brought into contact with the nanoscale
object. In some cases, the micropipette can be used to affect to
the intracellular potential of a cell. For example, the
intracellular potential of a cell may be held by a micropipette at
between -40 millivolts and -100 millivolts, between -60 millivolts
and -90 millivolts, between -50 millivolts and -80 millivolts, or
between -40 millivolts and -60 millivolts.
[0072] In some cases, the nanoscale object may have an amphiphilic
surface (e.g., a surface coated with phospholipid) that can
chemically interact with the lipid bilayer. In some embodiments,
the amphiphilic surface may decrease the amount of energy needed
for the lipid bilayer to rearrange around at least a portion of the
nanoscale object (i.e., fuse with nanoscale object).
[0073] In some embodiments, when a nanoscale object interacts with
a lipid bilayer, a portion of the nanoscale object may extend
completely through the lipid bilayer. As a non-limiting example, a
nanoscale object may penetrate the cell membrane such that a
portion of the nanoscale object is in contact with the cytosol of
the cell. In further embodiments, a nanoscale object may penetrate
more than one lipid bilayer (i.e., at least two lipid bilayers).
For example, a nanoscale object may penetrate the cell membrane of
a cell and another membrane inside the cell (e.g., the membrane of
an organelle). In some embodiments, a nanoscale object may be in
contact with the two or more lipid bilayers. Those of ordinary
skill in the art would be able to manipulate a cell and/or a
nanoscale object such that the cell and nanoscale object are
brought into contact with each other. Advantageously, the nanoscale
objects described herein may be fabricated to a size that minimally
disrupts a cell membrane.
[0074] As discussed in more detail below, a device comprising a
plurality of nano scale objects (i.e., at least two nanoscale
objects) may be used to penetrate a lipid bilayer at multiple
regions. In some embodiments, the plurality of nanoscale objects
may penetrate a lipid bilayer essentially simultaneously.
[0075] In another aspect, a nanoscale object may be configured with
an electrical circuit. For example, in some embodiments, the
nanoscale object may be connected to an AC or DC power source. In
some embodiments, a device may be fabricated that includes a
substrate on which is disposed a plurality of nanoscale objects. A
substrate may have disposed thereon at least two nanoscale objects,
at least 10 nanoscale objects, at least 100 nanoscale objects, at
least 1000 nanoscale objects, or even more. The nanoscale objects
may be spaced at any suitable distance from each other. In some
embodiments, the nanoscale objects are spaced such that on average
a single cell contacts only one nanoscale object at a time. In
other embodiments, the nanoscale objects may be spaced such that a
plurality of nanoscale objects can be in contact with a cell
essentially simultaneously. For example, a cell may be in contact
with at least two nanoscale objects, at least 10 nanoscale objects,
at least 100 nanoscale objects, at least 1000 nanoscale objects, or
even more. In some embodiments, a substrate may be flexible. For
example, the substrate may comprise a polymer, such as SU-8. In
some embodiments, a flexible substrate may be advantageous since a
nanoscale object attached to the flexible substrate may be flexed
in response to an external stimulus. For example, a nanoscale
object attached to a substrate that rises off the substrate from a
first point that is attached to the substrate such that a second
point on the nanoscale object is at a first distance from the
surface of the substrate (e.g., height) may be flexed to vary the
distance between the surface of the substrate and the second point
on the nanoscale object. For instance, a glass micropipette can be
pressed on and/or retracted from the nanoscale object to vary the
distance between the second point on the nanoscale object and the
substrate surface. A flexible substrate may be advantageous, for
example, when probing a moving cell with the nanoscale object. For
example, when probing a beating (i.e., pulsating) cardiomyocyte,
the flexible substrate can allow the nanoscale object to flex with
the movement of the cell. This property can be advantageous since
it can reduce the probability of the nanoscale object breaking.
Additionally, this property can reduce the probability of the
nanoscale object causing damage to the cell (e.g., tears to the
membrane). Examples of systems and methods involving flexible
substrates and nanoscale objects can also be seen in U.S.
application Ser. No. 10/995,075, filed Nov. 22, 2004, entitled
"Nanoscale Arrays, Robust Nanostructures, and Related Devices," by
Whang, et al., published as U.S. Pat. Apl. Pub. No. 2005-0253137 on
Nov. 17, 2005, incorporated herein by reference.
[0076] In some embodiments, a device comprising a plurality of
nanoscale objects may be used for multiplex assays. For example, a
device can be used to assay a plurality of cells essentially
simultaneously. In another example, a device may be used to assay a
plurality of regions of a cell essentially simultaneously. Such an
assay may be advantageous for determining, for example, how
electrical potential inside a cell varies between a first region
and a second region.
[0077] Nanoscale objects of the invention can be used to probe
biological materials, such as cells, using a variety of techniques.
U.S. Pat. No. 7,301,199, issued Nov. 27, 2007 to Lieber, et al.,
and U.S. Pat. No. 7,129,554, issued Oct. 31, 2006 to Lieber, et
al., both incorporated herein by reference, describe techniques for
making and using nanoscale objects, including arranging nanoscale
objects in devices for determination of various species. Some of
those techniques can be useful for probing biological species such
as cells in accordance with the present invention.
[0078] A nanoscale object in contact with a lipid bilayer may be
used to communicate electrically, e.g., for determination of some
aspect of the lipid bilayer or a related cell. For example, the
nanoscale object may be capable of sending and/or receiving an
electrical current, and/or passing an electrical current through
the nanowire that may be modified for determination. Generally, a
cell may be probed by determining a signal or a change in a signal,
such as electrical potential or electrical current. The signal
amplitude, shape, sign, etc. may all be detected individually or
together. In some embodiments, the signal corresponding to a first
property (i.e., electrical potential or electrical current) may be
correlated with a second property. For example, the electrical
potential detected by the nanoscale object may be correlated with
pH. Thus, in some embodiments, the nanoscale object may be used to
detect the pH within a cell. In some embodiments, the signal
detected by the nanoscale object may be recorded. In some
embodiments, the nanoscale object may transmit and/or receive a
current greater than 0.1 picoamps, greater than 1 picoamp, greater
than 10 picoamps, greater than 100 picoamps, greater than 1
nanoamp, greater than 10 nanoamps, greater than 100 nanoamps,
greater than 1 microamp, greater than 10 microamps, greater than
100 microamps, or even more. In some embodiments, the nanoscale
object transmit a current between 0.1 picoamps and 100 microamps,
between 0.1 picoamps and 100 picoamps, between 10 picoamps and 10
nanoamps, between 1 nanoamp and 1 microamp, or between 100 nanoamps
and 100 microamps.
[0079] In some cases, the nanoscale object may be capable of
detecting an electric potential, e.g., the nanoscale object may be,
or include, a field effect transistor (FET). In some embodiments,
the nanoscale object may be a two terminal FET device. In some
cases, the nanoscale object may detect an electric potential of
greater than 0.1 microvolts, greater than 1 microvolt, greater than
10 microvolts, greater than 100 microvolts, greater than 1
millivolt, greater than 10 millivolts, greater than 100 millivolts,
greater than 1 volt, or even greater. In some embodiments, the
nanoscale object may detect an electric potential between 0.1
microvolts and 1 volt, between 0.1 microvolts and 100 microvolts,
between 10 microvolts and 10 millivolts, or between 1 millivolt and
1 volt. In the case of a FET device, the nanoscale object may, in
some embodiments, perform as a gate in the transistor. The
nanoscale object may allow an increase or decrease in the flow of
current between the source and drain of the transistor in response
to a threshold electrical potential. The threshold electrical
potential may be within any of the voltage ranges listed above. In
some embodiments, the nanoscale object can detect the electrical
potential intracellularly by being in contact with the cytosol.
[0080] In some embodiments, the nanoscale object may used to be
communicate electrically with a cell. For example, the nanoscale
object may be used to transmit a current to the cell. In some
embodiments, the transmitting a current to a cell may induce an
action potential.
[0081] In some cases, the nanoscale object may be used to determine
electrical activity in a cell. Advantageously, the nanoscale object
may be used in certain embodiments in place of a patch clamp and/or
voltage clamp. In some embodiments, the nanoscale object may be
used to determine electric activity in a cell using field effect.
Also advantageously, it is believed that the nanoscale objects are
less disruptive to cells because of the small size of the nanoscale
objects and/or surface functionalization of the nanoscale objects,
at least in some cases.
[0082] In some embodiments, a nanoscale object may be used to probe
a micelle, a liposome, a cell, or any entity having an interface.
An interface may be formed, for example, by an amphiphilic material
(e.g., a phospholipid or surfactant). In another example, an
interface may be formed by oil-water mixture, such as in an
emulsion. In some embodiments, the interface in a lipid bilayer. A
nanoscale object may be used to probe any type of cell. The cell
may be an isolated cell or may be part of a group of cells, such as
in a tissue or biofilm. A cell may be a human cell, an animal cell,
a non-human mammalian cell, a bacterial cell, a eukaryotic cell, or
an archaeal cell. Non-limiting examples of cells include neurons,
cardiomyocytes, muscle cells, and pancreatic beta cells.
[0083] In another aspect, the devices and methods described herein
may be used as a tool for drug discovery. For example, an assay may
be set up where cells are treated with one or more candidate drugs
(e.g., a library of drug candidates) and the effect of each drug
candidate, alone or in combination with another drug candidate
and/or known drug (i.e., pharmaceutical agent), on the electrical
activity of the cell may be determined.
[0084] As mentioned, in some embodiments, the nanoscale object
(e.g., nanoscale wire) may have at least one "kink." As used
herein, a kink is a relatively sharp transition or turning between
a first substantially straight portion of a wire and a second
substantially straight portion of a wire. The transition may be
defined by a transition region linearly defined along the length of
the wire, where the region has a maximum linear length that is less
than about 5% of the linear length of the average of the first and
second substantially straight portion of the regions immediately
surrounding the transition region. In some cases, the transition
region may have a linear length that is less than about 5%, less
than about 3%, less than about 1%, less than about 0.5%, less than
about 0.3%, less than about 0.1%, less than about 0.03%, or less
than about 0.01% of the linear length of the substantially straight
portions surrounding the transition region. As an illustrative
example, with reference to FIG. 8, wire 5 includes a first straight
portion 10 on the left and a second straight portion 20 on the
right of a transition region 30. The linear length of portion 10 is
"a," and the linear length of portion 20 is "b." The maximum linear
length of portion 30, the transition or "kinked" region, is the
longest linear length through this region, given by "c" in FIG.
8.
[0085] In some embodiments, a semiconductor nanoscale wire
comprises or consists essentially of one crystallographic
orientation. For example, the semiconductor nanoscale wire may
comprise or consist essentially of a <110> crystallographic
orientation, a <112> crystallographic orientation, or a
<1120> crystallographic orientation. It should be noted that
the kinked region need not have the same crystallographic
orientation as the rest of the semiconductor nanoscale wire. For
instance, the semiconductor nanoscale wire may have a <112>
crystallographic orientation while containing one or more kinked
regions having a <110> crystallographic orientation. Those of
ordinary skill in the art will be able to determine the
crystallographic orientation of a nanoscale wire, or portions
thereof, using routine techniques such as lattice-resolved TEM
images or selected area electron diffraction (SAED) patterns using
the nanoscale wire.
[0086] In some embodiments, at least some of the kinked regions of
a semiconductor nanoscale wires may be at an angle of about
120.degree.. Without wishing to be bound by any theory, the
approximately 120.degree. angle may be due to the fact that certain
of the semiconductor nanoscale wires may consist essentially of the
same crystallographic orientation; due to the packing of atoms
along the same crystallographic orientation, only certain kink
angles, such as 120.degree. angles, may be allowed in order to
ensure that the nanoscale wire exhibits the same crystallographic
orientation on both sides of the kink. In addition, as discussed
below, in some embodiments, during growth of the nanoscale wire,
only certain growth directions may be allowed, and the growth
directions are at 120.degree. relative to each other. In addition,
in certain embodiments, due to the same crystallographic
orientation, the semiconductor nanoscale wire may be substantially
planar, i.e., the semiconductor nanoscale wire can be generally
contained within a plane, even in embodiments where multiple kinked
regions are found in the nanoscale wire.
[0087] Non-limiting examples of such planar nanoscale wires are
shown in FIGS. 1C and 1D. Kinking angles in a semiconductor
nanoscale wire may be determined using any suitable technique,
e.g., using imaging techniques such as TEM imaging techniques.
[0088] In some embodiments, a nanoscale object (e.g., nanoscale
wire) may comprise more than one kink, as described above.
Referring now to FIG. 9A, 100 depicts nanoscale object having a
"cis" conformation, where 110 and 112 are on the same side. Also as
shown in FIG. 9A, 102 depicts a nanoscale object having a "trans"
conformation, where 113 and 114 are on opposite sides. In some
cases, a combination of approximately 120.degree. angle kinks can
be used to form nanoscale objects of various shapes. For example,
100 comprises two approximately 120.degree. angle kinks that result
in 100 having an approximately 60.degree. angle kink. In another
example, 101 comprises three approximately 120.degree. angle kinks
that result in 101 having an approximately 0.degree. angle kink.
One of ordinary skill in the art will recognize that nanoscale
objects with other shapes and angles can be fabricated in other
embodiments.
[0089] In some cases, at least a portion of a nanoscale wire may be
doped, and the nanoscale wire may be doped using techniques such as
those known to ordinary skill in the art. Non-limiting examples of
such doping techniques are discussed below. In one set of
embodiments, different portions of the nanoscale wire may be doped
or undoped, and/or different portions of the nanoscale wire may
have different dopants, and/or different concentrations of dopants.
For instance, in some embodiments, the nanoscale wire may include a
first portion having a first doping characteristic, and a second
portion having a second doping characteristic. The first portion
and the second portion may be separated by one or more kinks within
the nanoscale wire. Non-limiting examples of methods of growing
such nanoscale wires are discussed below.
[0090] Certain aspects of the invention are generally directed to
fabricating semiconductor nanoscale wires and other nanoscale
objects such as those described herein. Techniques useful for
fabricating nanoscale wires include, but are not limited to, vapor
phase reactions (e.g., chemical vapor deposition ("CVD") techniques
such as metal-catalyzed CVD techniques, catalytic chemical vapor
deposition ("C-CVD") techniques, organometallic vapor phase
deposition-MOCVD techniques, atomic layer deposition, chemical beam
epitaxy, etc.), solution phase reactions (e.g., hydrothermal
reactions, solvothermal reactions), physical deposition methods
(e.g., thermal evaporation, electron-beam evaporation, laser
ablation, molecular beam epitaxy), vapor-liquid-solid ("VLS")
growth techniques, laser catalytic growth ("LCG") techniques,
surface-controlled chemical reactions, or the like, for instance,
as disclosed in Ser. No. 10/196,337, entitled, "Nanoscale Wires and
Related Devices," filed Jul. 16, 2002, published as Publication No.
2003/0089899 on May 15, 2003, incorporated herein by reference. The
nanoscale wires may be either grown in place or deposited after
growth. For instance, the nanoscale wires may be grown on a
substrate using techniques such as photolithography, e.g., using
submicron photolithography, extreme-UV lithography or nanoimprint
lithography.
[0091] In certain embodiments, a nanoscale wire containing one or
more kinks can be grown using certain vapor-liquid-solid ("VLS")
growth techniques. For instance, in one set of embodiments, a
catalyst particle may be used to grow a first portion of a
nanoscale wire, for instance, by exposing the catalyst particle to
a first reactant, such as a gaseous reactant. Such a wire may be
axially extended in a first direction. Exposure of the catalyst
particle to the first reactant may then be stopped, which may stop
axial growth of the wire. The catalyst particle can then be
perturbed and/or supersaturated to restart growth of the wire. For
instance, the catalyst particle may be exposed to exposed to a
second reactant (which may be the same or different than the first
reactant) and supersaturated and/or nucleated to restart nanoscale
wire growth. In some cases, the direction of growth of the
nanoscale wire may be altered, for example, by altering the
direction of flow of the second reactant, relative to the first
reactant.
[0092] In some embodiments, the nanoscale wire may be doped during
growth of the wire, and in certain cases, the dopant may be
changed, e.g., added or removed, and/or the concentration of the
dopant may be changed, and/or the dopant may be removed and a
second dopant added, etc. Thus, as a non-limiting example, the
growing nanoscale wire may be exposed to a first dopant in the
first reactant and to a second dopant in the second reactant to
create a semiconductor nanoscale wire having a first portion having
a first doping characteristic, and a second portion having a second
doping characteristic, e.g., as previously described.
[0093] This process may also be repeated as many times as desired
to grow nanoscale wires having any suitable number of kinks. In
addition, the length of each of the substantially straight segments
may be controlled, for example, by controlling the length of time
the nanoscale wire is exposed to a reactant. In some embodiments,
the angle of the kink may be controlled by the crystallographic
orientation of the nanoscale wire, e.g., such that an angle of
about 120.degree. is created at the kink region, as described
above.
[0094] As mentioned, certain nanoscale wires may be grown using a
vapor-liquid-solid (VLS) mechanism. One feature of the VLS growth
process is that equilibrium phase diagrams can be used to select
catalysts and growth conditions, and thereby enable rational
synthesis of nanoscale wire materials. Semiconductor nanoscale
wires of the III-V materials GaAs, GaP, GaAsP, InAs, InP and InAsP,
the II-VI materials ZnS, ZnSe, CdS and CdSe, and IV-IV alloys of
SiGe can be synthesized in high yield and purity using VLS
techniques. Other semiconductors, such as GaAs and CdSe, can also
be grown. The nanoscale wires may be prepared as single crystals
with dimensions such as those described herein.
[0095] Generally, the size of the nanoscale wire is controlled, at
least in part, by the size of the catalyst particle used to grow
the nanoscale wire. The catalyst particle may be prepared using any
suitable technique, for example, using the LCG method, which uses
laser ablation to generate nanometer diameter catalytic clusters or
particles. This methodology allows the direct formation of adjacent
regions having different compositions within a nanoscale wire, such
as a p/n junction, and/or adjacent regions differing in
concentration of a particular element or composition. In these
techniques, a nanoparticle catalyst is used during growth of the
nanoscale wire, which may be further subjected to different
semiconductor reagents during growth. Alteration of the
semiconductor reagents may allow for the formation of abrupt or
gradual changes in the composition of the growing semiconductor
material, allowing heterostructured materials to be
synthesized.
[0096] Techniques for doping after growth of the nanoscale wires
may also be used, in addition to (or instead of) doping during
growth. For example, a nanoscale wire such as those described
herein may be first synthesized, then doped post-synthetically with
various dopants as discussed herein. For example, a p/n junction
can be created by introducing p-type and n-type dopants on a single
nanoscale wire. The p/n junction can then be further annealed to
allow the dopants to migrate further into the nanoscale wire to
form a bulk-doped nanoscale wire.
[0097] As mentioned, the nanoscale wire may be doped during growth
of the nanoscale wire. Doping the nanoscale wire during growth may
result in the property that the doped nanoscale wire is bulk-doped.
Furthermore, such doped nanoscale wires may be controllably doped,
such that a concentration of a dopant within the doped nanoscale
wire can be controlled and therefore reproduced consistently,
making possible the commercial production of such nanoscale wires.
Additionally, the dopant may be systematically altered during the
growth of the nanoscale wire, for example, so that the final
nanoscale wire has a first doped region comprising a first dopant
and a second doped region differing in composition from the first
region, for example, by comprising a second dopant, comprising the
first dopant at a different concentration, or omitting the first
dopant.
[0098] In some embodiments, dopants may be introduced during vapor
phase growth of nanoscale wires. For instance, laser vaporization
of a composite target composed of a desired material (e. g. silicon
or indium phosphide) and/or a catalytic material (e. g. gold) may
create a hot, dense vapor. The vapor may condense into liquid
nanoclusters through collision with a buffer gas. Growth may begin
when the liquid nanoclusters become supersaturated with the desired
phase and can continue as long as reactant is available. Growth may
terminate when the nanoscale wire passes out of the hot reaction
zone or when the temperature is decreased.
[0099] Vapor phase semiconductor reactants required for nanoscale
wire growth may be produced by laser ablation of solid targets,
vapor-phase molecular species, or the like. To create a single
junction within a nanoscale wire, the addition of the first
reactant may be stopped during growth, and then a second reactant
may be introduced for the remainder of the synthesis. Repeated
modulation of the reactants during growth may also be used, which
may produce nanoscale wire superlattices. Different catalysts
suitable for growth may be used, for example, a gold catalyst can
be used in a wide-range of III-V and IV materials. Nearly
monodisperse metal clusters or particles may be used to control the
diameter, and, through growth time, the length various
semiconductor nanoscale wires.
[0100] As another example, such methods may be used to create
nanoscale wires having a multishell configuration. For example, by
altering the synthetic conditions during growth, homogeneous
reactant decomposition may occur on the surface of the nanoscale
wire. Control of the synthetic conditions may lead to a shell
forming on the surface of at least a portion of the nanoscale wire,
and in some embodiments, the synthetic reaction conditions may be
controlled to cause the formation of a thin, uniform shell, a shell
having a thickness of one atomic layer, or less in some cases. In
other embodiments, by modulating or altering the reactants during
growth, more than one shell may be built up on the outer surface of
the nanoscale wire. As one example, a silicon nanoscale wire core
may be grown, and additional semiconductor materials may be
deposited onto at least a portion of the surface, for example, a
germanium shell, or a silicon shell doped with a dopant such as
boron, or other dopants as described elsewhere in this application.
The boundaries between the shells may be atomically abrupt, or may
be graduated in some fashion, depending on how reactants such as,
for example, silane, germane, or diborane are introduced into the
laser catalytic growth system. Arbitrary sequences of Si, Ge, and
alloy overlayers on both Si and Ge nanowire cores may also be
prepared. Other factors may also contribute to the growing
nanoscale wire, such as, for example, the reaction temperature, or
the sample position within the furnace. By varying these
parameters, the ratio of axial growth to radio growth may be
controlled as desired.
[0101] Any catalyst able to catalyze the production of nanoscale
wires may be used, e.g., as catalyst particles. Gold may be used in
certain embodiments. A wide range of other materials may also be
contemplated, for example, a transition metal such as silver,
copper, zinc, cadmium, iron, nickel, cobalt, and the like.
Generally, any metal able to form an alloy with the desired
semiconductor material, but does not form a more stable compound
than with the elements of the desired semiconductor material may be
used as the catalyst.
[0102] The buffer gas may be any inert gas, for example, N.sub.2 or
a noble gas such as argon. In some embodiments, a mixture of
H.sub.2 and a buffer gas may be used to reduce undesired oxidation
by residual oxygen gas.
[0103] A reactive gas used during the synthesis of the nanoscale
wire may also be introduced when desired, for example, ammonia for
semiconductors containing nitrogen, such as gallium nitride.
Nanoscale wires may also be flexibly doped by introducing one or
more dopants into the composite target, for example, a germanium
alloy during n-type doping of InP. The doping concentration may be
controlled by controlling the relative amount of doping element,
for example, between 0% and about 10% or about 20%, introduced in
the composite target.
[0104] Laser ablation may also be used to generate liquid
nanoclusters that subsequently define the size and/or direct the
growth direction of the nanoscale wires. The diameters of the
resulting nanoscale wires may be determined by the size of the
catalyst cluster or particle, which may be varied by controlling
the growth conditions, such as the pressure, the temperature, the
flow rate and the like. For example, lower pressure may produce
nanoscale wires with smaller diameters in certain cases. Further
diameter control may be performed by using uniform diameter
catalytic clusters or particles.
[0105] If uniform diameter nanoclusters (e.g., less than 10% or
less than 20% variation depending on the uniformity of the
nanoclusters) are used as the catalytic cluster, nanoscale wires
with uniform size (diameter) distribution can be produced in some
embodiments, where the diameter of the nanoscale wires is
determined by the size of the catalytic clusters. By controlling
the growth time or the position of the sample within the reactor,
nanoscale wires with different lengths and/or different shell
thicknesses may be grown.
[0106] Nanoscale wires having uniform diameters or size
distributions may be produced in embodiments where the diameter of
the nanoscale wire is determined by the size of the catalytic
cluster. For example, uniform diameter nanoclusters (for example,
having a variation of less than about 10% or less than about 20% in
the average diameter) may be used as the starting catalytic
clusters.
[0107] The diameters of the resulting nanoscale wires may be
determined by the size of the catalyst cluster, which in turn may
be determined using routine experiments that vary the growth
conditions, such as background pressure, temperature, flow rate of
reactants, and the like. For example, lower pressure generally
produces nanoscale wires with smaller diameters. Further diameter
control may be achieved by using uniform diameter catalytic
clusters.
[0108] The catalytic clusters or the vapor phase reactants may be
produced by any suitable technique. For example, laser ablation
techniques may be used to generate catalytic clusters or vapor
phase reactant that may be used. Other techniques may also be
contemplated, such as thermal evaporation techniques.
[0109] According to another aspect, semiconductor nanoscale wires
such as those described herein can be used in a variety of
electronic devices. Techniques for assembling one or more nanoscale
wires on a surface, e.g., as part of an electronic device, are
known to those of ordinary skill in the art, and include, but are
not limited to, electric field alignment, fluid flow, surface
regions that selectively attract nanoscale wires, biomolecular
recognition, SAMs, microcontact printing, chemically patterned
surfaces, or the like. Non-limiting examples of these and other
techniques are disclosed in Ser. No. 10/196,337, entitled,
"Nanoscale Wires and Related Devices," filed Jul. 16, 2002,
published as Publication No. 2003/0089899 on May 15, 2003,
incorporated herein by reference in its entirety.
[0110] For example, nanoscale wires such as those described herein
may be used in a wide variety of devices. Such devices may include
electrical devices, optical devices, optronic devices, spintronic
devices, mechanical devices or any combination thereof, for
example, optoelectronic devices, and electromechanical devices.
Functional devices assembled from the nanoscale wires of the
present invention may be used to produce various computer or device
architectures. Non-limiting examples of these and other devices are
disclosed in Ser. No. 10/196,337, entitled, "Nanoscale Wires and
Related Devices," filed Jul. 16, 2002, published as Publication No.
2003/0089899 on May 15, 2003, incorporated herein by reference.
[0111] The following definitions will aid in the understanding of
the invention. However, all definitions as used herein are solely
for the purposes of this application. These definitions should not
necessarily be imputed to other commonly-owned applications,
whether related or unrelated to this application.
[0112] Certain devices of the invention may include wires or other
components of scale commensurate with nanometer-scale wires, which
includes nanotubes and nanowires. In some embodiments, however, the
invention comprises articles that may be greater than nanometer
size (e. g., micrometer-sized). As used herein, "nanoscopic-scale,"
"nanoscopic," "nanometer-scale," "nanoscale," the "nano-" prefix
(for example, as in "nanostructured"), and the like generally
refers to elements or articles having widths or diameters of less
than about 1 micrometer, and less than about 100 nm in some cases.
In all embodiments, specified widths can be a smallest width (i.e.
a width as specified where, at that location, the article can have
a larger width in a different dimension), or a largest width (i.e.
where, at that location, the article has a width that is no wider
than as specified, but can have a length that is greater).
[0113] As used herein, the term "Group," with reference to the
Periodic Table, is given its usual definition as understood by one
of ordinary skill in the art. For instance, the Group II elements
include Mg and Ca, as well as the Group II transition elements,
such as Zn, Cd, and Hg. Similarly, the Group III elements include
B, Al, Ga, In and Tl; the Group IV elements include C, Si, Ge, Sn,
and Pb; the Group V elements include N, P, As, Sb and Bi; and the
Group VI elements include 0, S, Se, Te and Po. Combinations
involving more than one element from each Group are also possible.
For example, a Group II-VI material may include at least one
element from Group II and at least one element from Group VI, for
example, ZnS, ZnSe, ZnSSe, ZnCdS, CdS, or CdSe. Similarly, a Group
III-V material may include at least one element from Group III and
at least one element from Group V, for example GaAs, GaP, GaAsP,
InAs, InP, AlGaAs, or InAsP. Other dopants may also be included
with these materials and combinations thereof, for example,
transition metals such as Fe, Co, Te, Au, and the like.
[0114] As used herein, "nanoscopic-scale," "nanoscopic,"
"nanometer-scale," "nanoscale," the "nano-" prefix, and the like
generally refers to elements or articles having widths or diameters
of less than about 1 .mu.m, preferably less than about 100 nm in
some cases. In all embodiments, specified widths can be smallest
width (i.e. a width as specified where, at that location, the
article can have a larger width in a different dimension), or
largest width (i.e. where, at that location, the article's width is
no wider than as specified, but can have a length that is
greater).
[0115] As used herein, a "wire" generally refers to any material
having a conductivity of or of similar magnitude to any
semiconductor or any metal, and in some embodiments may be used to
connect two electronic components such that they are in electronic
communication with each other. For example, the terms "electrically
conductive" or a "conductor" or an "electrical conductor" when used
with reference to a "conducting" wire or a nanoscale wire, refers
to the ability of that wire to pass charge. Typically, an
electrically conductive nanoscale wire will have a resistivity
comparable to that of metal or semiconductor materials, and in some
cases, the electrically conductive nanoscale wire may have lower
resistivities, for example, a resistivity lower than about
10.sup.-3 Ohm m, lower than about 10.sup.-4 Ohm m, or lower than
about 10.sup.-6 Ohm m or 10.sup.-7 Ohm m.
[0116] A "nanoscopic wire" (also known herein as a
"nanoscopic-scale wire" or "nanoscale wire") generally is a wire,
that at any point along its length, has at least one
cross-sectional dimension and, in some embodiments, two orthogonal
cross-sectional dimensions less than 1 .mu.m, preferably less than
about 500 nm, preferably less than about 200 nm, more preferably
less than about 150 nm, still more preferably less than about 100
nm, even more preferably less than about 70, still more preferably
less than about 50 nm, even more preferably less than about 20 nm,
still more preferably less than about 10 nm, and even less than
about 5 nm. In other embodiments, the cross-sectional dimension can
be less than 2 nm or 1 nm. In one set of embodiments, the nanoscale
wire has at least one cross-sectional dimension ranging from 0.5 nm
to 200 nm. In some cases, the nanoscale wire is electrically
conductive.
[0117] In some embodiments, the nanoscale wire is cylindrical. In
other embodiments, however, the nanoscale wire can be faceted,
i.e., the nanoscale wire may have a polygonal cross-section. Where
nanoscale wires are described having, for example, a core and a
shell, the above dimensions generally relate to those of the core.
The cross-section of a nanoscopic wire may be of any arbitrary
shape, including, but not limited to, circular, square,
rectangular, annular, polygonal, or elliptical, and may be a
regular or an irregular shape. The nanoscale wire may be solid or
hollow.
[0118] Any nanoscale wire or other nanoscale object can be used in
any of the embodiments described herein, including carbon
nanotubes, molecular wires (i.e., wires formed of a single
molecule), nanorods, nanowires, nanowhiskers, organic or inorganic
conductive or semiconducting polymers, and the like, unless
otherwise specified. Other conductive or semiconducting elements
that may not be molecular wires, but are of various small
nanoscopic-scale dimension, also can be used in some instances,
e.g. inorganic structures such as main group and metal atom-based
wire-like silicon, transition metal-containing wires, gallium
arsenide, gallium nitride, indium phosphide, germanium, cadmium
selenide structures. A wide variety of these and other nanoscale
wires can be grown on and/or applied to surfaces in patterns useful
for electronic devices in a manner similar to technique described
herein involving nanoscale wires, without undue
experimentation.
[0119] The nanoscale objects (e.g., nanoscale wires), in some
cases, may be formed having dimensions of at least about 1
micrometer, at least about 3 micrometers, at least about 5
micrometers, or at least about 10 micrometers or about 20
micrometers in length, and can be less than about 100 nm, less than
about 80 nm, less than about 60 nm, less than about 40 nm, less
than about 20 nm, less than about 10 nm, or less than about 5 nm in
thickness (height and width). The nanoscale wires may have an
aspect ratio (length to thickness) of greater than about 2:1,
greater than about 3:1, greater than about 4:1, greater than about
5:1, greater than about 10:1, greater than about 25:1, greater than
about 50:1, greater than about 75:1, greater than about 100:1,
greater than about 150:1, greater than about 250:1, greater than
about 500:1, greater than about 750:1, or greater than about 1000:1
or more in some cases.
[0120] As used herein, a "nanotube" (e.g. a carbon nanotube) is a
nanoscopic wire that is hollow, or that has a hollowed-out core,
including those nanotubes known to those of ordinary skill in the
art. "Nanotube" is abbreviated herein as "NT." Nanotubes are used
as one example of small wires for use in the invention and, in
certain embodiments, devices of the invention include wires of
scale commensurate with nanotubes.
[0121] A "nanowire" (e. g. comprising silicon or another
semiconductor material) is a nanoscopic wire that is generally a
solid wire, and may be elongated in some cases. Preferably, a
nanowire (which is abbreviated herein as "NW") is an elongated
semiconductor, i. e., a nanoscale semiconductor. A "non-nanotube
nanowire" is any nanowire that is not a nanotube. In one set of
embodiments of the invention, a non-nanotube nanowire having an
unmodified surface is used in any arrangement of the invention
described herein in which a nanowire or nanotube can be used.
[0122] Many nanoscopic wires as used in accordance with the present
invention are individual nanoscopic wires. As used herein,
"individual nanoscopic wire" means a nanoscopic wire free of
contact with another nanoscopic wire (but not excluding contact of
a type that may be desired between individual nanoscopic wires,
e.g., as in a crossbar array). For example, an "individual" or a
"free-standing" article may, at some point in its life, not be
attached to another article, for example, with another nanoscopic
wire, or the free-standing article maybe in solution. This is in
contrast to nanotubes produced primarily by laser vaporization
techniques that produce materials formed as ropes having diameters
of about 2 nm to about 50 nm or more and containing many individual
nanotubes (see, for example, Thess, et al., "Crystalline Ropes of
Metallic Carbon Nanotubes," Science, 273:483-486 (1996)). This is
also in contrast to conductive portions of articles which differ
from surrounding material only by having been altered chemically or
physically, in situ, i.e., where a portion of a uniform article is
made different from its surroundings by selective doping, etching,
etc. An "individual" or a "free-standing" article is one that can
be (but need not be) removed from the location where it is made, as
an individual article, and transported to a different location and
combined with different components to make a functional device such
as those described herein and those that would be contemplated by
those of ordinary skill in the art upon reading this
disclosure.
[0123] As used herein, an "elongated" article (e. g. a
semiconductor or a section thereof) is an article for which, at any
point along the longitudinal axis of the article, the ratio of the
length of the article to the largest width at that point is greater
than 2:1. This ratio is termed the "aspect ratio."
[0124] In some embodiments, at least a portion of a nanoscopic wire
may be a bulk-doped semiconductor. As used herein, a "bulk-doped"
article (e.g. an article, or a section or region of an article) is
an article for which a dopant is incorporated substantially
throughout the crystalline lattice of the article, as opposed to an
article in which a dopant is only incorporated in particular
regions of the crystal lattice at the atomic scale, for example,
only on the surface or exterior. For example, some articles such as
carbon nanotubes are typically doped after the base material is
grown, and thus the dopant only extends a finite distance from the
surface or exterior into the interior of the crystalline lattice.
It should be understood that "bulk-doped" does not define or
reflect a concentration or amount of doping in a semiconductor, nor
does it necessarily indicate that the doping is uniform. In
particular, in some embodiments, a bulk-doped semiconductor may
comprise two or more bulk-doped regions. Thus, as used herein to
describe nanoscopic wires, "doped" refers to bulk-doped nanoscopic
wires, and, accordingly, a "doped nanoscopic (or nanoscale) wire"
is a bulk-doped nanoscopic wire. "Heavily doped" and "lightly
doped" are terms the meanings of which are clearly understood by
those of ordinary skill in the art. In some cases, one or more
regions may comprise a single monolayer of atoms ("delta-doping").
In certain cases, the region may be less than a single monolayer
thick (for example, if some of the atoms within the monolayer are
absent). As a specific example, the regions may be arranged in a
layered structure within the nanoscale wire, and one or more of the
regions may be delta-doped or partially delta-doped.
[0125] As used herein, a "width" of an article is the distance of a
straight line from a point on a perimeter of the article, through
the center of the article, to another point on the perimeter of the
article. As used herein, a "width" or a "cross-sectional dimension"
at a point along a longitudinal axis of an article is the distance
along a straight line that passes through the center of a
cross-section of the article at that point and connects two points
on the perimeter of the cross-section. The "cross-section" at a
point along the longitudinal axis of the article is a plane at that
point that crosses the article and is orthogonal to the
longitudinal axis of the article. The "longitudinal axis" of an
article is the axis along the largest dimension of the article.
Similarly, a "longitudinal section" of an article is a portion of
the article along the longitudinal axis of the article that can
have any length greater than zero and less than or equal to the
length of the article. Additionally, the "length" of an elongated
article is a distance along the longitudinal axis from end to end
of the article.
[0126] As used herein, a "cylindrical" article is an article having
an exterior shaped like a cylinder, but does not define or reflect
any properties regarding the interior of the article. In other
words, a cylindrical article may have a solid interior or may have
a hollowed-out interior. Generally, a cross-section of a
cylindrical article appears to be circular or approximately
circular, but other cross-sectional shapes are also possible, such
as a hexagonal shape. The cross-section may have any arbitrary
shape, including, but not limited to, square, rectangular, or
elliptical. Regular and irregular shapes are also included.
[0127] As used herein, a first article (e. g., a nanoscopic wire or
larger-sized structure) "coupled" to a second article is disposed
such that the first article either physically contacts the second
article or is proximate enough to the second article to influence a
property (e. g., an electrical property, an optical property, or a
magnetic property) of the second article. The term "electrically
coupled" when used with reference to a nanoscopic wire and an
analyte or another moiety such as a reaction entity, refers to an
association between any of the analyte, other moiety, and the
nanoscopic wire such that electrons can move from one to the other,
or in which a change in an electrical characteristic of one can be
determined by the other. This may include electron flow between
these entities, or a change in a state of charge, oxidation state,
redox potential, and the like. As examples, electrical coupling can
include direct covalent linkage between the analyte or other moiety
and the nanoscopic wire, indirect covalent coupling (e.g. via a
linking entity), direct or indirect ionic bonding, or other types
of bonding (e.g. hydrophobic bonding). In some cases, no actual
bonding may be required and the analyte or other moiety may simply
be contacted with the nanoscopic wire surface. There also need not
necessarily be any contact between the nanoscopic wire and the
analyte or other moiety, in embodiments where the nanoscopic wire
is sufficiently close to the analyte to permit electron tunneling
or other field effects between the analyte and the nanoscopic
wire.
[0128] As used herein, an "array" of articles (e.g., nanoscopic
wires) comprises a plurality of the articles, for example, a series
of aligned nanoscale wires, which may or may not be in contact with
each other. As used herein, a "crossed array" or a "crossbar array"
is an array where at least one of the articles contacts either
another of the articles or a signal node (e.g., an electrode).
[0129] As used herein, a "semiconductor" is given its ordinary
meaning in the art, i.e., an element having semiconductive or
semi-metallic properties (i.e., between metallic and non-metallic
properties). An example of a semiconductor is silicon. Other
non-limiting examples include elemental semiconductors, such as
gallium, germanium, diamond (carbon), tin, selenium, tellurium,
boron, phosphorous, or compound semiconductors such as CdS. The
semiconductor may be undoped or doped (e.g., p-type or n-type). As
used herein, a "single crystal" item (e.g., a semiconductor) is an
item that has covalent bonding, ionic bonding, or a combination
thereof throughout the item. Such a single crystal item may include
defects in the crystal, but is distinguished from an item that
includes one or more crystals, not ionically or covalently bonded,
but merely in close proximity to one another.
[0130] In some embodiments, the invention may be part of a system
constructed and arranged to determine an analyte in a sample to
which the nanoscopic wire is exposed. "Determine," and similar
terms in this context, means to determine the quantity and/or
presence of the an entity such as an analyte in a sample.
Determining steps may include, for example, electronic
measurements, piezoelectric measurements, electrochemical
measurements, electromagnetic measurements, photodetections,
mechanical measurements, acoustic measurements, gravimetric
measurements and the like. The presence of an analyte can be
determined by determining a change in a characteristic in a
nanoscopic wire, for example, an electrical characteristic or an
optical characteristic, and this change may be detectable.
"Determining" may refer to detecting or quantifying interaction
between species, e.g., detection of binding between two
species.
[0131] The term "reaction entity" refers to any entity that can
interact with another entity such as analyte (which can be a
chemical or biological species, e.g.) in such a manner to cause a
detectable change in a property of a nanoscopic wire. The reaction
entity may enhance the interaction between the nanoscopic wire and
the analyte, or generate a new chemical species that has a higher
or lower affinity to the nanoscopic wire, or to enrich the analyte
around the nanoscopic wire. The reaction entity can comprise a
binding partner to which the analyte binds. The reaction entity,
when it comprises a binding partner, can comprise a specific
binding partner of the analyte. For example, the reaction entity
may be a nucleic acid, an antibody, a sugar, a carbohydrate, or a
protein. In other embodiments, the reaction entity may be a
polymer, a catalyst, or a quantum dot. A reaction entity that
includes a catalyst may catalyze a reaction involving the analyte,
resulting in a product that causes a detectable change in the
nanoscopic wire, for example, via binding to an auxiliary binding
partner of the product electrically coupled to the nanoscopic wire.
Another examplary reaction entity is a reactant that reacts with
the analyte, producing a product that can cause a detectable change
in the nanoscopic wire. The reaction entity may define at least a
portion of a shell or a coating on or surrounding at least a part
of the nanoscopic wire. As one example, the shell may include a
polymer that recognizes molecules in, for example, a gaseous or
liquid sample, causing a change in the conductivity of the polymer
which, in turn, causes a detectable change in the nanoscopic wire.
In some cases, the reaction entity may comprise a nanoparticle, for
example, a nanoparticle having binding partners immobilized
thereto.
[0132] The term "quantum dot" is given its ordinary meaning in the
art, and generally refers to semiconductor or metal nanoparticles
(for example, a cadmium selenide nanoparticle) that absorb light
and re-emit light in a different color. The wavelength of the
emitted light may depend on the size of the quantum dot. For
example, a 2 nm quantum dot may be able to emit green light, while
a 5 nm quantum dot may be able to emit red light.
[0133] As used herein, "attached to," in the context of a species
relative to another species or to a surface of an article, means
that the species is chemically or biochemically linked via covalent
attachment, attachment via specific biological binding (e.g.,
biotin/streptavidin), coordinative bonding such as chelate/metal
binding, or the like. For example, "attached" in this context
includes multiple chemical linkages, multiple chemical/biological
linkages, etc.
[0134] The term "binding partner" refers to a chemical or
biological species, such as a protein, antigen, antibody, small
molecule, etc., that can undergo binding with another entity, e.g.
an analyte, or its respective "binding partner." The term includes
specific, semi-specific, and non-specific binding partners, as
known to those of ordinary skill in the art. As one example,
Protein A is usually regarded as a "non-specific" or semi-specific
binder. The term "specifically binds," when referring to a binding
partner (e.g., a protein, a nucleic acid, an antibody, or the
like.), may refer to a reaction that is determinative of the
presence and/or identity of one or more other members of the
binding pair in a mixture of heterogeneous molecules (e.g.,
including proteins and other biologics). Thus, for example, in the
case of a receptor/ligand binding pair, the ligand would
specifically and/or preferentially select its receptor from a
complex mixture of molecules, or vice versa. Other examples include
an enzyme that would specifically bind to its substrate, a nucleic
acid that would specifically bind to its complement, or an antibody
that would specifically bind to its antigen. Other examples include
nucleic acids that specifically bind or hybridize to their
complements, antibodies that specifically bind to their antigens,
and the like. The binding may be by one or more of a variety of
mechanisms including, but not limited to, ionic interactions,
covalent interactions, hydrophobic interactions, van der Waals
interactions, or the like.
[0135] The term "fluid" generally refers to a substance that tends
to flow and to conform to the outline of its container. Typically,
fluids are materials that are unable to withstand a static shear
stress. When a shear stress is applied to a fluid, it experiences a
continuing and permanent distortion. Typical fluids include liquids
and gasses, but may also include free flowing solid particles,
viscoelastic fluids, and the like.
[0136] The term "sample" can be any cell, tissue, or fluid that can
be derived from or originates from a biological source (a
"biological sample"), or other similar media, biological or
non-biological, and that can be evaluated in accordance with the
invention, such as a bodily fluid, environmental matter, water, or
the like. A sample can include, but is not limited to, a biological
sample drawn from an organism (e.g. a human, a non-human mammal, an
invertebrate, a plant, a fungus, an algae, a bacteria, a virus,
etc.); a sample drawn from food designed for human consumption, a
sample including food designed for animal consumption such as
livestock feed, milk; an organ donation sample, a sample of blood
destined for a blood supply; a sample from a water supply, and the
like. One example of a sample is a sample drawn from a human or
animal to determine the presence or absence of a specific nucleic
acid sequence.
[0137] A "sample suspected of containing" a particular component
means a sample with respect to which the content of the component
is unknown. For example, a fluid sample from a human suspected of
having a disease, such as a neurodegenerative disease or a
non-neurodegenerative disease, but not known to have the disease,
defines a sample suspected of containing neurodegenerative disease.
"Sample," in this context, includes naturally-occurring samples,
such as physiological samples from humans or other animals, samples
from food, livestock feed, and the like. Typical samples taken from
humans or other animals include tissue biopsies, cells, whole
blood, serum or other blood fractions, urine, ocular fluid, saliva,
cerebro-spinal fluid, fluid or other samples from tonsils, lymph
nodes, needle biopsies, etc.
[0138] The terms "polypeptide," "peptide," and "protein," may be
used interchangeably herein to refer to a polymer of amino acid
residues. The terms generally apply to amino acid polymers in which
one or more amino acid residues is a naturally occurring or
artificially created amino acid. The term also includes variants on
the traditional peptide linkage joining the amino acids making up
the polypeptide, such as an ester linkage.
[0139] The terms "nucleic acid," "oligonucleotide," and their
grammatical equivalents herein generally refer to at least two
nucleotides covalently linked together. A nucleic acid of the
present invention is preferably single-stranded or double stranded,
and may generally contain phosphodiester bonds, although in some
cases, as outlined below, nucleic acid analogs are included that
may have alternate backbones, comprising, for example,
phosphoramide (Beaucage et al. (1993) Tetrahedron 49(10):1925 and
references therein); Letsinger (1970) J. Org. Chem. 35:3800;
Sprinzl et al. (1977) Eur. J. Biochem. 81: 579; Letsinger et al.
(1986) Nucl. Acids Res. 14: 3487; Sawai et al. (1984) Chem. Lett.
805, Letsinger et al. (1988) J. Am. Chem. Soc. 110: 4470; and
Pauwels et al. (1986) Chemica Scripta 26: 1419), phosphorothioate
(Mag et al. (1991) Nucleic Acids Res. 19:1437; and U.S. Pat. No.
5,644,048), phosphorodithioate (Briu et al. (1989) J. Am. Chem.
Soc. 111:2321, O-methylphophoroamidite linkages (see Eckstein,
Oligonucleotides and Analogues: A Practical Approach, Oxford
University Press), and peptide nucleic acid backbones and linkages
(see Egholm (1992) J. Am. Chem. Soc. 114:1895; Meier et al. (1992)
Chem. Int. Ed. Engl. 31: 1008; Nielsen (1993) Nature, 365: 566;
Carlsson et al. (1996) Nature 380: 207). Other analog nucleic acids
include those with positive backbones (Denpcy et al. (1995) Proc.
Natl. Acad. Sci. USA 92: 6097; non-ionic backbones (U.S. Pat. Nos.
5,386,023, 5,637,684, 5,602,240, 5,216,141 and 4,469,863; Angew.
(1991) Chem. Intl. Ed. English 30: 423; Letsinger et al. (1988) J.
Am. Chem. Soc. 110:4470; Letsinger et al. (1994) Nucleoside &
Nucleotide 13:1597; Chapters 2 and 3, ASC Symposium Series 580,
"Carbohydrate Modifications in Antisense Research," Ed. Y. S.
Sanghui and P. Dan Cook; Mesmaeker et al. (1994), Bioorganic &
Medicinal Chem. Lett. 4: 395; Jeffs et al. (1994) J. Biomolecular
NMR 34:17; Tetrahedron Lett. 37:743 (1996)) and non-ribose
backbones, including those described in U.S. Pat. Nos. 5,235,033
and 5,034,506, and Chapters 6 and 7, ASC Symposium Series 580,
Carbohydrate Modifications in Antisense Research, Ed. Y. S. Sanghui
and P. Dan Cook. Nucleic acids containing one or more carbocyclic
sugars are also included within the definition of nucleic acids
(see Jenkins et al. (1995), Chem. Soc. Rev. pp. 169-176). Several
nucleic acid analogs are described in Rawls, C & E News Jun. 2,
1997 page 35. These modifications of the ribose-phosphate backbone
may be performed, for example, to facilitate the addition of
additional moieties such as labels, or to increase the stability
and half-life of such molecules in physiological environments.
Similarly, "polynucleotides" or "oligonucleotides" may generally
refer to a polymer of nucleotides, which may include natural
nucleosides (for example, adenosine, thymidine, guanosine,
cytidine, uridine, deoxyadenosine, deoxythymidine, deoxyguanosine
and deoxycytidine), nucleoside analogs (for example,
2-aminoadenosine, 2-thiothymidine, inosine, pyrrolopyrimidine,
3-methyladenosine, C5-bromouridine, C5-fluorouridine,
C5-iodouridine, C5-propynyluridine, C5-propynylcytidine,
C5-methylcytidine, 7-deazaadenosine, 7-deazaguanosine,
8-oxoadenosine, 8-oxoguanosine, O6-methylguanosine or
2-thiocytidine), chemically or biologically modified bases (for
example, methylated bases), intercalated bases, modified sugars
(2'-fluororibose, arabinose, or hexose), or modified phosphate
groups (for example, phosphorothioates or 5'-N-phosphoramidite
linkages).
[0140] As used herein, an "antibody" refers to a protein or
glycoprotein consisting of one or more polypeptides substantially
encoded by immunoglobulin genes or fragments of immunoglobulin
genes. The recognized immunoglobulin genes include, for example,
the kappa, lambda, alpha, gamma, delta, epsilon and mu constant
region genes, as well as other immunoglobulin variable region
genes. Light chains may be classified as either kappa or lambda.
Heavy chains may be classified as gamma, mu, alpha, delta, or
epsilon, which in turn may define the immunoglobulin classes, for
example, IgG, IgM,
[0141] IgA, IgD and IgE, respectively. A typical immunoglobulin
(antibody) structural unit may be a tetramer. Each tetramer may be
composed of two identical or similar pairs of polypeptide chains,
each pair having one "light" (about 25 kD) and one "heavy" chain
(about 50-70 kD). The N-terminus of each chain may define a
variable region of about 100 to 110 or more amino acids primarily
responsible for antigen recognition. The terms variable light chain
(VL) and variable heavy chain (VH) refer to these light and heavy
chains, respectively, and are well-known to those of ordinary skill
in the art. Antibodies may exist as intact immunoglobulins or as a
number of well characterized fragments produced by digestion with
various peptidases. Thus, as one example that would be understood
by one of ordinary skill in the art, pepsin may digest an antibody
below (i.e. toward the Fc domain) the disulfide linkages in the
hinge region to produce F(ab)'2, a dimer of Fab which itself is a
light chain joined to V.sub.H-C.sub.H1 by a disulfide bond. The
F(ab)'2 may be reduced under mild conditions to break the disulfide
linkage in the hinge region thereby converting the (Fab')2 dimer
into an Fab' monomer. The Fab' monomer may be a Fab with part of
the hinge region (see, Paul (1993) Fundamental Immunology, Raven
Press, N.Y. for a more detailed description of other antibody
fragments). While various antibody fragments may be defined in
terms of the digestion of an intact antibody, one of skill will
appreciate that such fragments may be synthesized de novo either
chemically, by utilizing recombinant DNA methodology, by "phage
display" methods (see, e.g., Vaughan et al. (1996) Nature
Biotechnology, 14(3): 309-314, and PCT/US96/10287) or other similar
techniques. Antibodies may also include single chain antibodies,
e.g., single chain Fv (scFv) antibodies in which a variable heavy
and a variable light chain are joined together (directly or through
a peptide linker) to form a continuous polypeptide.
[0142] As used herein, "plurality" means two or more.
[0143] As used herein, a "set" of items may include one or more of
such items.
[0144] As used herein, the terms "comprising," "including,"
"carrying," "having," "containing," "involving," and the like are
to be understood to be open-ended, i.e., to mean including but not
limited to.
[0145] The present invention, in many embodiments, includes
nanoscopic wires, each of which can be any nanoscopic wire,
including nanorods, nanowires, organic and inorganic conductive and
semiconducting polymers, nanotubes, semiconductor components or
pathways and the like. Other nanoscopic-scale conductive or
semiconducting elements that may be used in some instances include,
for example, inorganic structures such as Group IV, Group III/Group
V, Group II/Group VI elements, transition group elements, or the
like, as described below. For example, the nanoscale wires may be
made of semiconducting materials such as silicon, indium phosphide,
gallium nitride and others.
[0146] The nanoscale wires may also include, for example, any
organic, inorganic molecules that are polarizable or have multiple
charge states. For example, nanoscopic-scale structures may include
main group and metal atom-based wire-like silicon, transition
metal-containing wires, gallium arsenide, gallium nitride, indium
phosphide, germanium, or cadmium selenide structures.
[0147] The nanoscale wires may include various combinations of
materials, including semiconductors and dopants. The following are
non-comprehensive examples of materials that may be used as
dopants. For example, the dopant may be an elemental semiconductor,
for example, silicon, germanium, tin, selenium, tellurium, boron,
diamond, or phosphorous. The dopant may also be a solid solution of
various elemental semiconductors. Examples include a mixture of
boron and carbon, a mixture of boron and P(BP.sub.6), a mixture of
boron and silicon, a mixture of silicon and carbon, a mixture of
silicon and germanium, a mixture of silicon and tin, or a mixture
of germanium and tin.
[0148] In some embodiments, the dopant or the semiconductor may
include mixtures of Group IV elements, for example, a mixture of
silicon and carbon, or a mixture of silicon and germanium. In other
embodiments, the dopant or the semiconductor may include a mixture
of a Group III and a Group V element, for example, BN, BP, BAs, AN,
AlP, AlAs, AlSb, GaN, GaP, GaAs, GaSb, InN, InP, InAs, or InSb.
Mixtures of these may also be used, for example, a mixture of
BN/BP/BAs, or BN/AlP. In other embodiments, the dopants may include
alloys of Group III and Group V elements. For example, the alloys
may include a mixture of AlGaN, GaPAs, InPAs, GaInN, AlGaInN,
GaInAsP, or the like. In other embodiments, the dopants may also
include a mixture of Group II and Group VI semiconductors. For
example, the semiconductor may include ZnO, ZnS, ZnSe, ZnTe, CdS,
CdSe, CdTe, HgS, HgSe, HgTe, BeS, BeSe, BeTe, MgS, MgSe, or the
like. Alloys or mixtures of these dopants are also be possible, for
example, (ZnCd)Se, or Zn(SSe), or the like. Additionally, alloys of
different groups of semiconductors may also be possible, for
example, a combination of a Group II-Group VI and a Group III-Group
V semiconductor, for example, (GaAs).sub.x(ZnS).sub.1-x. Other
examples of dopants may include combinations of Group IV and Group
VI elemnts, such as GeS, GeSe, GeTe, SnS, SnSe, SnTe, PbO, PbS,
PbSe, or PbTe. Other semiconductor mixtures may include a
combination of a Group I and a Group VII, such as CuF, CuCl, CuBr,
CuI, AgF, AgCl, AgBr, AgI, or the like. Other dopant compounds may
include different mixtures of these elements, such as BeSiN.sub.2,
CaCN.sub.2, ZnGeP.sub.2, CdSnAs.sub.2, ZnSnSb.sub.2, CuGeP.sub.3,
CuSi.sub.2P.sub.3, Si.sub.3N.sub.4, Ge.sub.3N.sub.4,
Al.sub.2O.sub.3, (Al,Ga,In).sub.2(S,Se,Te).sub.3, Al.sub.2CO,
(Cu,Ag)(Al,Ga,In,Tl,Fe)(S,Se,Te).sub.2 and the like.
[0149] For Group IV dopant materials, a p-type dopant may be
selected from Group III, and an n-type dopant may be selected from
Group V, for example. For silicon semiconductor materials, a p-type
dopant may be selected from the group consisting of B, Al and In,
and an n-type dopant may be selected from the group consisting of
P, As and Sb. For Group III-Group V semiconductor materials, a
p-type dopant may be selected from Group II, including Mg, Zn, Cd
and Hg, or Group IV, including C and Si. An n-type dopant may be
selected from the group consisting of Si, Ge, Sn, S, Se and Te. It
will be understood that the invention is not limited to these
dopants, but may include other elements, alloys, or materials as
well.
[0150] Controlled doping of nanoscale wires can be carried out to
form, e.g., n-type or p-type semiconductors. One set of embodiments
involves use of at least one semiconductor, controllably-doped with
a dopant (e.g., boron, aluminum, phosphorous, arsenic, etc.)
selected according to whether an n-type or p-type semiconductor is
desired. A bulk-doped semiconductor may include various
combinations of materials, including other semiconductors and
dopants. For instance, the nanoscopic wire may be a semiconductor
that is doped with an appropriate dopant to create an n-type or
p-type semiconductor, as desired. As one example, silicon may be
doped with boron, aluminum, phosphorous, or arsenic. In various
embodiments, this invention involves controlled doping of
semiconductors selected from among indium phosphide, gallium
arsenide, gallium nitride, cadmium selenide. Dopants including, but
not limited to, zinc, cadmium, or magnesium can be used to form
p-type semiconductors in this set of embodiments, and dopants
including, but not limited to, tellurium, sulfur, selenium, or
germanium can be used as dopants to form n-type semiconductors from
these materials. These materials may define direct band gap
semiconductor materials and these and doped silicon are well known
to those of ordinary skill in the art. The present invention
contemplates use of any doped silicon or direct band gap
semiconductor materials for a variety of uses.
[0151] Nanotubes that may be used in the present invention include
single-walled nanotubes (SWNTs) that exhibit unique electronic, and
chemical properties that may be particularly suitable for molecular
electronics. Structurally, SWNTs may be formed of a single graphene
sheet rolled into a seamless tube with a diameter that may be, for
example, on the order of about 0.5 nm to about 5 nm, and a length
that can exceed about 10 .mu.m, about 20 .mu.m, or more in some
cases. Depending on diameter and helicity, SWNTs may behave as a
one-dimensional metal or a semiconductor material, and may also be
formed as a mixture of metallic and semiconducting regions. Methods
of manufacture of nanotubes, including SWNTs, and characterization
are known. Methods of selective functionalization on the ends
and/or sides of nanotubes also are known, and the present invention
makes use of these capabilities for use in molecular electronics.
The basic structural and electronic properties of nanotubes can be
used to create connections or input/output signals, and nanotubes
have a size consistent with molecular or nanoscopic-scale
architecture.
[0152] The present invention contemplates, in one aspect, a
nanoscale wire, for example, with a smallest width of less than 500
nm, having two or more regions having different compositions. The
regions may be positioned radially, as in a core/shell arrangement,
or longitudinally from each other. Combinations of these
arrangements are also possible.
[0153] Each regions may have any shape or dimension, as long as at
least one of the regions is nanoscopically-sized. For example, the
region may have a smallest dimension of less than 1 .mu.m, less
than 100 nm, less than 10 nm, or less than 1 nm. In some cases, one
or more regions may comprise a single monolayer of atoms
("delta-doping"). In certain cases, the region may be less than a
single monolayer thick (for example, if some of the atoms within
the monolayer are absent).
[0154] As used herein, regions differing in composition may
comprise different materials or elements, or may comprise the same
materials or elements, but at different ratios or concentrations.
Each region may be of any size or shape within the wire, for
example, the regions may be adjacently positioned along the
longitudinal axis of the nanoscale wire. The junctions may be, for
example, a p/n junction, a p/p junction, an n/n junction, a p/i
junction (where i refers to an intrinsic semiconductor), an n/i
junction, an i/i junction, or the like. The junction may also be a
Schottky junction. The junction may also be a
semiconductor/semiconductor junction, a semiconductor/metal
junction, a semiconductor/insulator junction, a metal/metal
junction, a metal/insulator junction, an insulator /insulator
junction, or the like. The junction may also be a junction of two
materials, a doped semiconductor to a doped or an undoped
semiconductor, or a junction between regions having different
dopant concentrations. The junction may also be a defected region
to a perfect single crystal, an amorphous region to a crystal, a
crystal to another crystal, an amorphous region to another
amorphous region, a defected region to another defected region, an
amorphous region to a defected region, or the like.
[0155] More than two regions may be present, and these regions may
have unique compositions or may comprise the same compositions. As
one example, a wire may have a first region having a first
composition, a second region having a second composition, and a
third region having a third composition or the same composition as
the first composition. Specific non-limiting examples include
gallium arsenide/gallium phosphide compositionally modulated
superlattices containing from 2 to 21 layers, or
n-silicon/p-silicon and n-indium phosphide/p-indium phosphide
modulation doped nanoscale wires.
[0156] The regions of the nanoscale wire may be distinct from each
other with minimal cross-contamination, or the composition of the
nanoscale wire may vary gradually from one region to the next. The
regions may be both longitudinally arranged relative to each other,
or radially arranged (e.g., as in a core/shell arrangement) on the
nanoscale wire. As one example, the nanoscale wire may have
multiple regions of alternating semiconductor materials arranged
longitudinally, each having a segment length of about 500 nm. In
another example, a nanoscale wire may have two regions having
different compositions arranged longitudinally, surrounded by a
third region or more having a composition different from that of
the other regions. As a specific example, the regions may be
arranged in a layered structure within the nanoscale wire, and one
or more of the regions may be delta-doped or partially
delta-doped.
[0157] In some embodiments, the junction between two differing
regions (e.g., between different longitudinal regions of a core or
shell, or between a core and shell, or between two different
shells) may be "atomically-abrupt," where there is a sharp
transition at the atomic scale between two adjacent regions that
differ in composition. However, in other embodiments, the junction
between two differing regions may be more gradual. For example, the
"overlap region" between the adjacent regions may be a few
nanometers wide, for example, less than about 10 nm, less than
about 20 nm, less than about 40 nm, less than about 50 nm, less
than about 100 nm, or less than about 500 nm. In certain
embodiments, the overlap region between a first region having a
composition and a second region having a composition different from
the first region (i.e., different concentrations or different
species) can be defined as the distance between where the
composition of the overlap region ranges between about 10 vol % and
about 90 vol % of the composition of the first region, with the
remainder having a complementary amount of the composition of the
second region. In certain embodiments of the invention, nanoscale
wires having more than one junction between two regions having
different compositions are also contemplated. For example, a
nanoscale wire may have 2, 3, 4, or more overlap regions. The
number of periods and the repeat spacing may be constant or varied
during growth.
[0158] In some embodiments, a gradual change in composition between
two adjacent regions may relieve strain and may enable the defect
free junctions and superlattices. However, in other embodiments,
atomically-abrupt interfaces may be desirable, for example, in
certain photonic and electronic applications. The nature of the
interface between the two adjacent regions may be controlled by any
suitable method, for example, by using different nanocluster
catalysts or varying the growth temperature when reactants are
switched during synthesis. Nanoscale wires having atomically abrupt
regions may be fabricated, for example, by reducing the diameter of
the nanoscale wire, for example, by reducing the size of the
starting nanocluster, or by controlling exposure of the growing
wire to dopant gases, for example, by selectively purging or
evacuating the region surrounding the wire between different gas
exposures or reaction conditions. All of these embodiments can be
provided with one, or multiple shells. These shells can be of the
same or different composition relative to each other, and any of
the shells can be of the same composition of a segment of the core,
or of a different composition, or can contain the same or different
concentration of a dopant as is provided in a section of the core.
The shells may be grown using any suitable growth technique, for
example, including the techniques described herein, such as CVD or
LCG.
[0159] In some embodiments, devices make particular use of adjacent
regions having different compositions within a nanoscale wire, for
example, p-type and n-type semiconductor regions. A p/n junction
may be defined by at least one n-type semiconductor and at least
one p-type semiconductor positioned adjacent to each other within
the nanoscale wire, where at least one portion of each region
contacts at least one portion of the other region, and each
semiconductor including portions that do not contact the other
component.
[0160] In various embodiments, the doping of semiconductors in a
nanoscale object (e.g., wire) may be controlled and altered. In
certain embodiments, the nanoscale wires may be produced using
techniques that allow for direct and controlled growth of the
nanoscale wires. The direct growth of doped nano scale wires may
eliminate the need to use lithographic steps during production of
the nanoscale wire, thus facilitating the "bottom-up" assembly of
complex functional structures.
[0161] Light-emission sources are provided in which electrons and
holes may combine to emit light. One embodiment of a light-emission
source includes at least one p/n junction, in particular, a p/n
junction within a single, free-standing nanoscale wire. When
forward-biased (i.e., positive charge applied to the p-type region
and a negative charge applied to the n-type region), electrons flow
toward the junction in the n-type region and holes flow toward the
junction in the p-type region. At the p/n junction, holes and
electrons may combine, emitting light. Other techniques may be used
to cause one or more nanoscale wires, or other semiconductors to
emit light, as described below in more detail.
[0162] At the size scale of the invention (nanoscale) the
wavelength of light emission may be controlled by controlling the
size of the p/n junction, for example, the overlap region between
the p-type region and the n-type region, the diameter of the
nanoscale wire or by controlling the size of at least one, and
preferably both components in embodiments having configurations
involving crossed wires. Where nanowires are used, a nanowire with
a larger smallest dimension will provide emission at a lower
frequency. For example, in the case of a doped indium phosphide
wire, at size scales associated with typical fabrication processes,
the material may emit at 920 nm, depending on the dopant. At the
size scales of the present invention, the wavelength of emission
may be controlled to emit at wavelengths shorter than 920 nm, for
example between 920 and 580 nm. Wavelengths can be selected within
this range, such as 900, 850, 800, 750, 700 nm, etc., depending
upon the wire size.
[0163] The nanoscale wires may also exhibit polarization anisotropy
in some embodiments. The polarization anisotropy may arise from the
large dielectric contrast inherent to the nanoscale wires having
two or more regions having different compositions. In contrast,
mixing of valence bands due to quantum confinement yields smaller
polarization ratios (i.e., less than about 0.60) in single-region
nanoscale wires. Thus, polarization-sensitive nanoscale
photodetectors may be constructed using the nanoscale wires of the
present invention, which may be used in integrated photonic
circuits, near-field imaging, or other high-resolution or
high-speed detectors.
[0164] The conductance (G) of an individual nanoscale wire may
increase by about 2 to 3 orders of magnitude with increasing
excitation power density in some cases. In some embodiments,
polarization-sensitive photodetectors in which an individual
nanoscale wire serves as the detection element may be constructed.
These photodetectors may have a reproducible photoconductivity with
a nearly instantaneous response time (i.e., with a response time of
less than about 1 s, preferably less than about 1 ms, more
preferably less than about 1 .mu.s, still more preferably less than
about 1 ns, and even more preferably less than about 1 ps, and even
more preferably still less than about 1 fs. Preferably, the
photoconductivity may also exhibit polarization anisotropy, where
the parallel excitation is over an order of magnitude larger than
the perpendicular excitation. Quantitatively, the photoconductivity
anisotropy ratio,
.sigma.=(G.sub..parallel.-G.sub..perp.)/(G.sub..parallel.+G.sub..perp.),
where G.sub..parallel. is the conductance with parallel excitation
and G.sub..perp. is the conductance with perpendicular excitation,
may be between 0.91.+-.0.07, with some nanodetectors exhibiting the
theoretical maximum polarization of 0.96 in the case of certain
indium phosphide wires. The active device nanoscale wire element of
the present invention may also be sensitive to multiple wavelengths
of light.
[0165] In some embodiment, information-recording devices may be
fabricated based on semiconducting nanoscale wires. In certain
embodiments, switching memory may be achieved based on the
observation that the conductance of these semiconducting nanoscale
wires can change significantly upon either a gate or bias voltage
pulse when the surface of the nanoscale wires are appropriately
modified, for example, with molecules, functional groups, or
nanocrystals. Other properties of the nanoscale wire may also be
used to record memory, for example, but not limited to, the redox
state of the nanoscale wire, mechanical changes, magnetic changes,
induction from a nearby field source, and the like.
[0166] Specifically, with respect to changes in conductance,
subjection to positive or negative gate or bias voltage pulses may
cause the change of charge states in the molecules or nanocrystals,
and induces the device to make a fully reversible transition
between low and high resistance states. The different states may
hysterically persist in the set state, even after the voltage
source is deactivated. This feature (change in electrical
properties upon voltage pulse) may enable the fabrication of
electrically erasable and rewritable memory switching devices in
which the reversible states are indicated by the conductance of the
nanoscale wires. In addition, the memory switching devices may be
assembled specifically from nanoscale material building blocks, and
may not be created in planar materials by lithography.
[0167] The following documents are incorporated herein by
reference: U.S. patent application Ser. No. 09/935,776, filed Aug.
22, 2001, entitled "Doped Elongated Semiconductors, Growing Such
Semiconductors, Devices Including Such Semiconductors, and
Fabricating Such Devices," by Lieber, et al., published as U.S.
Patent Application Publication No. 2002/0130311 on Sep. 19, 2002;
U.S. patent application Ser. No. 10/196,337, filed Jul. 16, 2002,
entitled "Nanoscale Wires and Related Devices," by Lieber, et al.,
now U.S. Pat. No. 7,301,199, issued Nov. 27, 2007; and U.S. patent
application Ser. No. 12/310,764, filed Mar. 6, 2009, entitled
"Branched Nanoscale Wires," by Lieber, et al.
[0168] The following examples are intended to illustrate certain
embodiments of the present invention, but do not exemplify the full
scope of the invention.
EXAMPLE 1
[0169] This example illustrates rational design and synthesis of 2D
multiply-kinked nanowires (FIG. 1A), where kinks are introduced at
defined positions during growth. These hierarchical nanowires were
built-up from a "secondary building unit" ("SBU") of two straight
single-crystalline arms connected by one fixed 120.degree. angle
joint (FIG. 1A). Two <112>.sub.c or <110>.sub.c vectors
in a cubic crystal structure, or two <11-20>.sub.h or
<1-100>.sub.h vectors in a hexagonal structure could form the
120.degree. joint when rotating about the <111>.sub.c and
<0001>.sub.h zone axes, respectively (FIG. 1A; FIG. 6). FIG.
1A shows a schematic of a coherently kinked nanowire and the
secondary building unit (SBU) which contains two arms and one
joint. The multiply-kinked nanowires (middle panel) were derived
from the corresponding 1D nanowire by introducing the joints at the
points indicated by dashed lines (upper panel). The subscript c and
h denote cubic and hexagonal structures, respectively.
[0170] In this example, SBU formation involved three main steps
during nanocluster-catalyzed growth (FIG. 1B); (A) axial growth of
a 1D nanowire arm segment, (B) purging of gaseous reactants to
suspend nanowire elongation, and (C) supersaturation and nucleation
of nanowire growth following re-introduction of reactants. The
gradient accompanying the innermost arrows indicates the change of
silicon concentration in nanocluster catalyst during synthesis of a
kinked silicon nanowire. As illustrated for the example case of
silicon, the concentration of silicon-reactant dissolved in the
nanocluster catalyst dropped during purging and then reached a
maximum upon supersaturation. Steps (A)-(C) can also be iterated to
link a number of SBUs generating a 2D chain structure (FIG.
1A).
[0171] This approach is first illustrated with the synthesis of 2D
silicon nanowire chains. Roughly 80 nm diameter silicon nanowires
with dominant <112> axial orientation were synthesized by
gold nanocluster-catalyzed vapor-liquid-solid (VLS) methods (see
below and FIG. 7). Scanning electron microscope (SEM) images of a
typical kinked silicon nanowire structure (FIG. 1C, scale bar of 1
micrometer) produced by several iterations of the cycle discussed
above, designed to yield equal-length segments, illustrate several
features, as follows. The arrow highlights the position of the
nanocluster catalyst. Well-defined 2D kinked nanowire structures
were observed with nearly equal arm lengths, which were consistent
with the constant segment growth times, and uniform diameters.
Visible gold catalyst was visible at the nanowire tips (FIGS. 1C
and 1D), and appeared to show uniform diameters, indicating that
growth proceeded via the nanocluster-catalyzed VLS process during
synthesis. FIG. 1D is an SEM image of a multiply-kinked silicon
nanowire with decreasing arm segment lengths; scale bar is 1
micrometer. The growth durations were 30, 60, 90, 120, 150, and 180
s for segments 1 to 6, respectively. The arrow highlights the
position of the nanocluster catalyst. In addition, the joint angle
appeared to be 120.degree. and all SBUs appeared to be confined in
a single 2D plane (FIG. 1A). Also, the yield of such a kinked 2D
chain structure was higher than 40% for these 80 nm diameter
nanowires with purge times of 15 seconds, while the remaining
nanowires had a 1D morphology.
[0172] With respect to FIG. 6, FIG. 6A illustrates certain
crystallographic parameters for rational synthesis of kinked
semiconductor nanowires with cubic crystal structures. The group IV
atoms (e.g., silicon and germanium) were arranged in a "diamond
structure," while Group III(II) and Group V(VI) atoms adopted the
"zinc-blend" or "sphalerite" structural motifs. The left panel in
FIG. 6A depicts a schematic electron diffraction (ED) pattern from
a cubic single crystal recorded along the [111] zone axis. Light
and dark arrows mark a pair of <112> and <110>
directions, respectively, with an angle of 120.degree. separating
identical directions in the (111) plane. This discussion is focused
on nanowires with <112> orientations and those defined by the
diamond crystal structure (e.g., silicon and germanium). The
schematic [-112] zone ED pattern (middle panel), which corresponds
to an ED pattern recorded from the cross section of a
<112>-oriented silicon nanowire, identifies a single
<111> axis. Inducing rotation about this <111> axis at
controlled points in a nanowire would yield a 2D multi-kinked
superstructures (right panel). It should also be noted that
kink-arm growth was generally coherent, that is with preservation
of the original <112> orientation of the silicon
nanowire.
[0173] FIG. 6B illustrates certain crystallographic parameters for
rational synthesis of kinked semiconductor nanowires with hexagonal
crystal structures, for example, the "wurtzite" structures of the
II-VI and III-V semiconductors cadmium sulfide and gallium nitride.
A schematic ED pattern recorded along the [0001] zone axis (left
panel) shows pairs of <11-20> or <1-100> directions
with 120.degree. between identical directions in the (0001) plane.
Similar to the discussion of FIG. 6A, there was a single
<0001> axis in <11-20>-oriented nanowires as visualized
in the schematic [2-1-10] zone ED pattern 1 (middle panel). A 2D
multi-kinked superstructures of <11-20>-oriented wurtzite
nanowires (right panel) was formed by rotating about this
<0001> axis. In the ED patterns, the zone axis is denoted as
B, and x symbols mark double diffraction spots.
[0174] FIG. 7 shows growth orientation statistics for silicon
nanowires. The silicon nanowires were grown using 80 nm diameter
gold nanocluster catalysts at 455-460.degree. C. and 40 torr total
pressure. The flow rates of silane, phosphine and hydrogen were
1-2, 2-10 and 60 standard cubic centimeters per minute,
respectively. Transmission electron microscopy (TEM) imaging and
electron diffractions (ED) were used to identify the nanowire
orientations. Under these growth conditions, <112>-oriented
nanowires appeared to predominate.
EXAMPLE 2
[0175] To illustrate ab initio design and synthesis, in this
example, kinked silicon nanowires were prepared in which the arm
length was intentionally varied. A representative SEM image of a
structure with 6-distinct segment lengths (FIG. 1D) revealed that
the formation of well-defined SBU kinks appeared to be independent
of the constituent segment lengths within a range of at least
180-2500 nm that were investigated.
[0176] Analysis of the segment lengths in uniformly kinked nanowire
samples yielded a linear dependence of segment length on the axial
growth time (FIG. 1E), further supporting well controlled VLS
growth. In FIG. 1E, each diamond represents average segment length
data (error bars: .+-.1 standard deviation) from a sample
containing nanowires with uniform segment lengths between kinks.
The line is a linear fit to these data. The solid squares are data
points taken from the nanowire shown in FIG. 1D. The inset shows
growth pressure variation during kink synthesis. Solid spheres and
squares denote the start of purging and re-introduction of
reactants, respectively. The slope of the linear fit yielded a
nanowire axial growth rate of 870 nm/min under current steady state
conditions (FIG. 1E, inset; see also below). The differential
segment length data extracted from FIG. 1D was also plotted
(squares) and agreed with data acquired from the kinked nanowires
with uniform segments, demonstrating control for independent
syntheses and, correspondingly, the capability for ab initio design
and synthesis. It should also be noted that these results show that
segment length was determined by growth time.
EXAMPLE 3
[0177] This example shows the atomic level structure of the 2D
kinked nanowires using transmission electron microscopy (TEM). A
representative TEM image (FIG. 2A) of a multiply-kinked silicon
nanowire and selected area electron diffraction (SAED) patterns
recorded from nonadjacent joints (FIGS. 2B-2C) showed that this
nanostructure was single crystalline and that the arms and joints
appeared to be free of bulk dislocations and defects. FIG. 2A is a
bright-field TEM image of a multiply-kinked silicon nanowire; scale
bar corresponds to 1 micrometer. The region I and region II dashed
circles highlight nonadjacent kinks where diffraction data was
recorded. The yellow arrow highlights the position of the
nanocluster catalyst. FIG. 2B shows selected area electron
diffraction (SAED) patterns recorded from regions I and II in FIG.
2A. The SAED patterns were recorded along the <111> zone
axis. FIG. 2C is a TEM image of a single kink with crystallographic
directions and facets indicated by arrows and dashed lines,
respectively; the scale bar is 50 nm. The region I and region II
open squares highlight regions of the joint and one arm where high
resolution images were recorded.
[0178] The SAED patterns from kink positions I and II, which were
separated by about 3 micrometers and 2 intervening kinks, could be
indexed for the <111> zone axis and showed that the 2D chain
structure extended in the {111} plane. This also confirmed that the
segments grew along the <112> direction in a coherent manner.
These observations were consistent with FIG. 1A.
[0179] Lattice-resolved TEM images of a single kink from regions I
and II in FIG. 2C (FIGS. 2D, 2E, and 2F) further illuminate key SBU
features. The scale bars are 5 nm. Dashed lines and arrows denote
crystallographic planes and growth directions, respectively. The
images demonstrated that there are no atomic-scale twin defects or
stacking faults, showing a single crystal structure across the
complete arm-joint-arm junction. Furthermore, the SBU reported here
preserves crystallographic orientation and composition in arms over
multiple kinks. Also, the joint appeared to be a quasi-triangular
structure with {111} top/bottom facets and {112} side facets
joining the two arms. The outer nanowire edge facet appeared to
change during growth of the kink, following {110}.sub.arm to
{112}.sub.joint to {110}.sub.arm.
EXAMPLE 4
[0180] In this example, to show the mechanism and limits of the
single crystalline kinked junction formation, the kink frequency
was characterized as a function of certain parameters, including
nanowire diameter and purge time. The kink frequency was defined in
this particular example as
P.sub.kink=N.sub.k/N.sub.t=N.sub.k/(N.sub.k+N.sub.s), where
N.sub.t, N.sub.k and N.sub.s denoted the number of total designed
junctions, observed kink junctions, and observed straight and
node-like junctions, respectively. Under optimal growth conditions
(see below), both 80 and 150 nm silicon nanowires (FIG. 3A) showed
a high probability of kinks with a regular zigzag geometry. FIG. 3A
shows SEM images of 150 (upper) and 80 nm (lower) diameter kinked
silicon nanowires grown with periodic 15 s purges; scale bar is 1
micrometer.
[0181] When the purge time of step-B (FIG. 1B) was reduced to 3 s
or 1 s, nodes or incipient kinks (FIGS. 3B-3C) were observed at the
positions expected for kinks based on elongation time and growth
rate. FIGS. 3B and 3C are TEM images at low (FIG. 3B) and high
(FIG. 3C) magnification of one 80 nm diameter silicon nanowire
segment subjected to a 1 s purge. The stars mark incipient kinks or
nodes, and the dashed square corresponds to the region where FIG.
3C was recorded. Scale bars are 500 and 50 nm. Higher resolution
SEM or TEM defined the nodes as slightly larger diameter regions
with lengths of .about.50 nm.
[0182] A summary of results for 80 and 150 nm diameters obtained
for 1 s, 3 s, and 15 s purges (FIG. 3D) quantifies these
observations and shows that this reduced kink frequency with
decreasing purge times appeared to be more pronounced in larger
diameter nanowire samples. Each of these was averaged over at least
15 multiply-kinked nanowires. These results are consistent with
reactant depletion from the nanocluster catalyst being important
for kink formation since the relative depletion will be smaller at
fixed purge time in larger versus smaller diameter nanowires.
[0183] Overall, without wishing to be bound by any theory, the
above studies suggest kink formation may potentially be explained
by the step-wise model shown in FIG. 3E. Arrows 1-4 denote purge,
reintroduction of reactant, joint growth and subsequent arm growth,
respectively. In step 1 of this model, reactant is depleted from
the catalyst during the purge, and if the concentration is reduced
sufficiently, elongation will cease. When reactant is re-introduced
in step 2, the catalyst can become supersaturated and undergo
heterogeneous nucleation. For short purge times and larger diameter
nanowires, the reactant concentration is sufficient for elongation
to continue; however, this situation can lead to a flattening of
the catalyst nanodroplet and increase in nanowire diameter
consistent with formation of nodes (FIG. 3C, marked with stars). In
step 3, growth proceeds with preservation of the most stable {111}
facets, thus implying that the heterogeneous nucleation should
occur preferentially at the active {110} edges of the three phase
boundary. This model yields a transition from the <112> to
<110> direction about the <111> axis. This growth along
<110> is transient since this direction is not
thermodynamically favorable in this diameter regime (FIG. 7), and
in step 4, the kink is completed with a transition to another
<112> direction thus completing a single SBU with coherent
arm growth directions. <112> to <111> growth switching
was not observed in these kinked structures, possibly because the
growth of a <111> segment required the formation of six new
{112} facets and the disappearance of two stable {111} facets of
the initial <112> segment.
EXAMPLE 5
[0184] The model described in Example 4 may allow the design and
synthesis of specific structures in silicon nanowires and, more
generally, nanowire systems with distinct compositions. To
illustrate this point, in this example, (kink-node).sub.m and
(kink-node).sub.m(kink).sub.n modulated silicon nanowire structures
were designed and synthesized, where m and n are indices denoting
the number of times the structural unit's growth is repeated. 150
nm gold as catalysts were chosen, with 15 s and 1 s as purge
durations (FIG. 3D) for the growth of kinks and nodes,
respectively. Notably, SEM images of the (kink-node).sub.m
structure (FIGS. 3F, I and II) showed that the nodes (highlighted
with stars) were reproducibly inserted between kinks over multiple
modulations. FIG. 3F illustrates SEM images of 2D silicon nanowires
with modulated kinks and incipient kinks (starred nodes). I
corresponds to a designed (kink-node),, structure, II is zoom of
one node from the region indicated by the dashed yellow square in
I, and III corresponds to a, (kink-node).sub.m(kink).sub.n
structure, where m and n are integers. The scale bars in I, II and
III are 1, 0.2 and 1 .mu.m, respectively.
[0185] These results also showed that the formation of individual
kinks or nodes can be independent of adjacent elements and may be
controlled by growth conditions. This point and possible control is
further demonstrated by the synthesis of coherent (kink).sub.8 SBUs
following modulated (kink-node).sub.4 units (FIG. 3F, III).
Interestingly, the observation of coherent zigzag chain structures
suggests that "steering" of kinks is not random and might be due,
for example, to a minimization of stress or maintenance of the
centre-of-mass of the whole structure. These results highlight the
potential of this approach to generate in a predictable manner
complex 2D nanowire structures.
EXAMPLE 6
[0186] This model may also be used for the designed synthesis of 2D
kinked nanowire structures in other materials. For example, SEM
images (FIG. 4A) of Ge nanowires grown using the iterative approach
of FIG. 1A (see below) show nanowires with well-defined kinks,
where the kink angle, 120.degree., is consistent with that for the
SBU. TEM images (FIG. 4B) further demonstrated that the growth
direction of the arms of the 2D kinked Ge nanowires was along the
<112> direction. This also shows that the joint was single
crystalline. These structural details were consistent with the
features observed in kinked silicon nanowires as discussed in the
examples above (e.g., FIGS. 1 and 2). This model also shows the
arm-joint-arm kink SBU could be realized in very different
materials such as the wurtzite phase of the group II-VI
semiconductor CdS. Notably, designed iterative modulation of the
growth of <11-20> direction CdS nanowires may yield a regular
2D kinked structure with 120.degree. kink angle as shown in FIG.
4C. TEM images (FIG. 4D) demonstrated that the CdS 2D kinked
nanowire structure was single-crystalline with arms all along the
<11-20> direction of the wurtzite phase. This approach could
also be used for the designed synthesis of 2D kinked group III-V
nanowire materials such as GaN nanowires, potentially with almost
pure <11-20> orientation.
[0187] With respect to FIG. 4, FIG. 4A illustrates an SEM image of
one multiply kinked germanium nanowire; scale bar is 1 micrometer.
The dashed square highlights one SBU with a 120.degree.
arm-joint-arm angle. FIG. 4B illustrates a lattice-resolved TEM of
the joint region of a representative germanium nanowire kink; scale
bar is 5 nm. The inset highlights one SBU with arrows corresponding
to <112> growth directions and the square indicates the
region where the high-resolution image was recorded. The inset
scale bar is 50 nm. FIG. 4C is an SEM image of one multiply kinked
cadmium sulphide nanowire; scale bar is 1 micrometer. The dashed
square highlights one SBU with a 120.degree. arm-joint-arm angle.
FIG. 4D is a lattice-resolved TEM of the arm region of a
representative cadmium sulfide adjacent to the kink joint; scale
bar is 5 nm. The inset highlights two SBU with arrows corresponding
to <11-20> growth directions and the square indicates the
region where the high-resolution image was recorded. Inset scale
bar is 50 nm.
EXAMPLE 7
[0188] This example illustrates the use of approaches such as the
ones described above to generate more complex nanowires with
potentially unique function integrated at the nanoscale in the
topologically-defined points of the kinks. This I shown by
combining the iterative growth approach used in the previous
examples with additional modulation of dopant to vary electronic
characteristics in a well-defined manner with respect to the
kinks.
[0189] A kinked Si nanowire SBU with integrated n- and p-type arms
was synthesized by switching phosphine and diborane dopants during
the kink growth sequence (see below). Current-voltage (I-V) data
recorded on a representative single kink device (FIG. 5A) revealed
a current rectification in reverse bias with an onset at forward
bias voltage of about 0.6 V, consistent with the synthesis of a
well defined p-n diode within the kinked structure. The inset shows
an SEM image of the device structure. The scale bar is 2
micrometers. Moreover, an electrostatic force microscopy image of a
typical kinked p-n nanowire in reverse bias (FIG. 5B) showed that
the voltage drop occurs primarily at the designed p-n junction
localized and labeled by the kink during growth. In particular,
this figure is an electrostatic force microscopy image of a p-n
diode reverse-biased at 5 V. The AFM tip voltage was modulated by 3
V at the cantilever-tip resonance frequency. The signal brightness
was proportional to the nanowire device surface potential, and
showed an abrupt drop around the kink position. The dashed lines
mark the nanowire position.
EXAMPLE 8
[0190] This example illustrates the design and synthesis of
nanowires with distinct functionality at sequential kinks. A
representative atomic force microscopy image of a double kink
structure synthesized with n.sup.+ and n dopant profiles at the two
kink joints (FIG. 5C) showed that the characteristic SBU described
above appeared to be generally unaffected by multiple modulations
of dopant concentration. Notably, scanned gate microscopy data
(FIG. 5D) demonstrated enhanced (decreased) nanowire conductance as
the tip with positive (negative) gate potential was scanned across
the designed n-type segment immediately adjacent to the upper-left
kink junction, thus confirming the integration of an n-type
field-effect transistor at a well-defined and recognizable point on
the structure. The absence of gate response from the lower-right
kink junction (FIG. 5D-5E) further showed that the single
crystalline kink structure itself does not appear to alter the
electrical transport properties. FIGS. 5C-5E are AFM and scanning
gate microscopy images of one n.sup.+-kink-n.sup.+-kink-(n-n.sup.+)
dopant modulated double-kinked silicon nanowire structure. The
scale bar in FIG. 5C corresponds to 2 micrometers. The scanning
gate images were recorded with a V.sub.tip of 10 V (I, FIG. 5D) and
-10 V (II, FIG. 5E), respectively, and a V.sub.sd of 1 V. The dark
and bright regions correspond to reduced and enhanced conductance,
respectively. The dashed lines mark the nanowire position.
EXAMPLE 9
[0191] This example illustrates various methods used in Examples
1-8. Single-crystalline kinked nanowires were synthesized by the
nanocluster-catalyzed VLS method described herein. Silicon
nanowires were synthesized at 450-460.degree. C. using monodisperse
gold nanoclusters as catalysts, silane as the silicon reactant,
hydrogen as the carrier gas, and phosphine and diborane as the n-
and p-type dopants. The total pressure during growth was 40 torr
and the minimum pressure during the purge cycle was about
3.times.10.sup.-3 torr. These conditions yielded dominant growth
direction of <112> (FIG. 7), and it should be noted that Si
nanowires with <111> growth direction generally did not
exhibit kinks for conditions optimized for the SBU in <112>
oriented nanowires.
[0192] Germanium nanowires were synthesized with gold nanocluster
catalysts at 270-290.degree. C., using germane and other conditions
similar to silicon. Cadmium sulfide nanowires were grown in a
three-zone furnace by evaporating CdS power at 650-720.degree. C.,
with nanowire growth by gold nanocluster catalyzed VLS method at
550-500.degree. C. zone. The purge cycle for kinks in the Ge and
CdS nanowires was typically 15 s.
[0193] Devices for electrical transport measurements were
fabricated on silicon substrates (100 nm oxide/200 nm nitride,
0.005 Ohm cm resistivity, Nova Electronic Materials), where Ti/Pd
(1.5 nm/100 nm) contacts were defined by electron beam lithography
and deposited by thermal evaporation. Current-voltage (I-V) data
were recorded using a semiconductor parameter analyzer with a probe
station. Electrostatic force and scanned gate microscopy
measurements were carried out with a Digital Instruments Nanoscope
Ma MultiMode AFM and metal coated tips. The surface potential and
conductance maps were acquired in lift mode with a lift height of
40 and 20 nm, respectively.
[0194] Nanowire synthesis. Single-crystalline kinked nanowires were
synthesized by the nanocluster-catalyzed VLS method in quartz tube
connected to gas manifold and vacuum pump and heated by a
temperature controlled tube furnace. Monodisperse gold
nanoparticles (Ted Pella) were dispersed on SiO.sub.2/Si or
sapphire growth substrates, which were placed within the central
region of the quartz tube reactor. The silicon (Si) nanowires were
synthesized at 450-460.degree. C. using silane (SiH.sub.4) as the
silicon reactant source, hydrogen (H.sub.2) as the carrier gas, and
phosphine (PH.sub.3, 1,000 p.p.m. in H.sub.2) and diborane
(B.sub.2H.sub.6, 100 p.p.m. in H.sub.2) as the n- and p-type
dopants. In a typical synthesis of uniform n-type, 80 nm kinked
silicon nanowires, the flow rates of SiH.sub.4, PH.sub.3 and
H.sub.2 were 1-2, 2-10 and 60 standard cubic centimetres per
minute, respectively, and the total pressure was 40 torr and purge
duration was 15 s; the minimum pressure during the purge cycle was
about 3.times.10.sup.-3 torr. The dopant feed-in ratios
(silicon:boron/phosphorus) in kinked p-n silicon nanowires were
500:1 for both p- and n-type segments. In
n.sup.+-kink-n.sup.+-kink-(n-n.sup.+) dopant modulated silicon
nanowires, the silicon-phosphorus feed-in ratios were 200:1 and
10000:1 for n.sup.+- and n-type segments, respectively, and the
n-segment was grown for 30 s.
[0195] Germanium nanowires were synthesized at 270-290.degree. C.,
40 torr, with germane (GeH.sub.4, 10% in H.sub.2) and H.sub.2 as
the reactant and carrier gas, respectively.
[0196] Cadmium sulfide nanowires were grown in a three-zone furnace
by evaporating CdS power at 650-720.degree. C., with nanowire
growth by gold nanocluster catalyzed VLS method at 550-500.degree.
C. The purge cycle used to form kinks in the germanium and cadmium
sulphide nanowires was typically 15 s.
[0197] Structure characterization. Zeiss Ultra55/Supra55VP
field-emission SEMs and JEOL 2010 field emission TEM were used to
carry out SEM and TEM analyses, respectively. For sample
preparation, all kinked nanowires were gently sonicated in
isopropyl alcohol and dispersed onto heavily doped silicon
substrates (100 nm oxide/200 nm nitride, 1-10 Ohm cm resistivity,
Nova Electronic Materials, Carrollton, Tex.) or lacey carbon grids
(Ted Pella).
[0198] Device fabrication and measurement. Devices were fabricated
on silicon substrates (Nova Electronic Materials, n-type 0.005 Ohm
cm) with 100 nm thermal oxide and 200 nm silicon nitride at the
surface. Devices were defined by electron-beam lithography followed
by Ti/Pd (1.5 nm/100 nm) contact deposition in a thermal
evaporator. Current-voltage (I-V) data were recorded using an
Agilent semiconductor parameter analyzer (Model 4156C) with
contacts to devices made using a probe station (Desert Cryogenics,
Model TTP4). Electrostatic force microscopy and scanned gate
microscopy measurements were carried out with a Digital Instruments
Nanoscope IIIc MultiMode AFM and metal coated tips (Nanosensors,
PPP-NCHPt). The electrostatic force microscopy surface potential
maps and scanned gate microscopy conductance maps were acquired in
lift mode with lift heights of 40 and 20 nm, respectively.
[0199] In the surface potential measurements, the p-n diode was
reverse-biased at 5 V and the tip voltage was modulated by 3 V at
the resonance frequency. In scanned gate measurements, the tip
functions as a local gate V.sub.t=.+-.10 V, and the conductance
versus position provided a measure of local accumulation or
depletion of carriers in the device.
EXAMPLE 10
[0200] The example demonstrates fabrication of a two-terminal
semiconductor device for interfacing single cells intracellularly.
The device includes single crystalline kinked silicon nanowire
structures with sharp junction angles (FIG. 9A) that were
synthesized using a nanotectonic approach. Two or three 120.degree.
kinks with separation distances (L) less than 250 nm were
sequentially introduced during the nanocluster catalyzed chemical
vapour deposition process. A representative scanning electron
microscopy (SEM) image of an 80 nm diameter, doubly kinked nanowire
(FIG. 9B) shows well defined two adjacent 120.degree. kinks with
L.about.160 nm and an overall 60.degree. junction angle, consistent
with the schematic diagram (FIG. 9A, 100).
[0201] Similar to describing the molecule conformations, `cis` and
`trans` crystal conformations were introduced to delineate doubly
kinked nanowire structures where segments 110 and 112 are on the
same (FIG. 9A, 100) and different (FIG. 9A, 102) sides of segment
111, respectively. One step in synthesizing the kinked nanowire
structures with either 60.degree. or 0.degree. junction angles
(FIG. 9A, 100 and 101) instead of the open structure (FIG. 9A, 102)
was to grow the `cis` forming kinks controllably. Next, the segment
length (L) was varied from .about.700 to 50 nm for doubly kinked
silicon nanowires having a diameter of 80 nm. A plot of the
cis/(cis+trans) ratio as a function of L in these doubly kinked
structures (FIG. 9C) shows that the `cis` conformation became
dominant as L shrunk, and vice versa, indicating that sharp angle
kinked nanowire structures (FIG. 9A, 100 and 101) can be
selectively grown with reasonable yield. Significantly, the
diameter and segment length of the 60.degree. kinked silicon
nanowires can be pushed down to .about.18 and 15 nm (FIG. 9D, FIG.
13), respectively, suggesting a potential filamentous semiconductor
probe with dimensions smaller than microtubules in single cells.
Finally, dopant modulation in 60.degree. kinked nanowires was
achieved. Specifically, as used elsewhere in this example, a short
(.about.200 nm) and lightly doped n-type field effect transistor
(FET) was integrated near the tips of the 60.degree. kinked
nanowires, as confirmed by scanning gate microscopy measurement
(FIG. 14B).
[0202] To address the potential of ab initio design and synthesis,
kinked nanowire structures were prepared with double 60.degree.
junctions (FIG. 9E), integrated 60.degree. and 120.degree.
junctions (FIG. 9F), and integrated 0.degree. and 120.degree.
junctions (FIG. 9G). The segments that form `cis` conformation
(yellow stars) were shorter than 250 nm but were longer than 650 nm
for `trans` ones (magenta stars), consistent with the data shown in
FIG. 9C and demonstrating the conformation control for independent
syntheses.
[0203] A free-standing and flexible nanowire field effect
transistor device was designed for interfacing biological systems
in three-dimensions (3D) (FIG. 10A, FIG. 15, and Methods). The
approach to suspending the devices from the substrate utilized the
interfacial stress between different materials to bend and actuate
the micron-scale layered structures. The SEM and optical microscopy
images of one free-standing device (FIG. 10B) highlight several
important features. Firstly, the 60.degree. kinked nanowire (stars
on the left) was intact after fabrications with two terminals
sandwiched between epoxy micro-ribbons (stars in the middle) and
metal contacts (stars on the right), consistent with designs (FIG.
10A). Secondly, the tip height and angle (H, .theta.) (theta) of
the device in air and in water were (25 micrometers, 43.degree.)
and (38 micrometers, 90.degree.), respectively (FIG. 2B, II, III).
The larger bending of the device in water might be a result of
decrease in elastic modulus of epoxy ribbons and suggests that the
nanowire probe device is intrinsically flexible and can potentially
be triggered chemically. Thirdly, the probe orientation (H,
.theta.) could be tuned arbitrarily and reproducibly by changing,
e.g. the length of the free-standing part of hybrid structure (FIG.
15) and the thicknesses of each layers. Finally, the free-standing
FET devices could be stored in air for at least 8 months without
substantial change in probe orientations and electrical transport
properties.
[0204] Mechanically elastic and electrically robust probe devices
are of particular interest for a number of practical applications.
In this regard, a glass micropipette was used to vary the probe tip
height manually by pressing or lifting the soft epoxy backbones in
phosphate buffered saline (PBS) solution (FIG. 10C, inset) while
recording the device conductance and watergate sensitivity changes.
The free-standing, nanoscale FET probe devices normally show a
watergate sensitivity of 4-8 microsiemens/V in PBS solution without
deformations (FIG. 16A). Measurements of a typical device (FIG.
10C) yield a <20 nS conductance change within a .about.18
micrometer deflection in H, corresponding to a <0.31%
fluctuation in the total device conductance and a <3.2 mV
potential change in PBS solution. Likewise, the device sensitivity
remained stable with a maximum change of .about.0.15
microsiemens/V, a 2.4% variation of total watergate sensitivity. In
addition, both device orientation and electrical transport
properties recovered to their initial states after the micropipette
detached the probe device, and repetitive bending did not degrade
the device performance.
[0205] To show that the free-standing FET devices can serve as a 3D
`point` sensor for biological and chemical species, a pH sensing
cell comprising a microfluidic channel formed between a
poly(dimethylsiloxane) (PDMS) mold and the nanowire probe/substrate
was assembled (FIG. 10D, inset). Measurements of the calibrated
nanowire surface potential as a function of time and solution pH
(FIG. 10D) demonstrated that the potential increased stepwise with
discrete changes in pH from 7.5 to 6.7 and that the potential was
constant for a given pH. The pH sensitivity was .about.58 mV/pH,
which is close to the Nernstian limit. In addition, the changes in
surface potential were also reversible for increasing and/or
decreasing pH (FIG. 16B).
[0206] FIGS. 9A-9G. Synthesis of kinked silicon nanowire probes.
(A) Schematics of 60.degree. (top) and 0.degree. (middle)
multiply-kinked nanowires, and `cis` (top) and `trans` (bottom)
configurations in nanowire structures. 1, 2, and 3 denote three
sequential segments that are separated by two adjacent 120.degree.
kinks. L is the length of segment 2. (B) SEM image of a
doubly-kinked nanowire with `cis` configuration. (C)
cis/(cis+trans) vs. L plot. (D) Transmission electron microscopy
image of an ultrathin 60.degree. kinked nanowire. (E) SEM image of
a kinked nanowire with double 60.degree. junctions. (F) and (G) SEM
images of 60.degree. (F.) and 0.degree. (G) kinked nanowires with
extended arm configurations. Scale bars, 200 nm in (B), (E), (F),
and (G); 50 nm in (D).
[0207] FIGS. 10A-10D. Freestanding and flexible devices. (A)
Schematics of device fabrication. The patterned PMMA and SU-8 epoxy
micro-ribbons serve as sacrificial layer and flexible device
support, respectively. The dimensions of the lightly doped n-type
silicon segment are about 80.times.80.times.200 nm.sup.3. H and
.theta. (theta) are tip height and orientation, respectively. (B)
SEM image of an as-made device. Left, center, and right stars mark
the nanowire, SU-8, and metal layers, respectively. The scale bar
is 5 micrometers. (C) Device conductance and sensitivity under
external bending. The deflections were recorded as the change in
tip height H. Inset, experiment schematics. (D) High performance 3D
nanoscale pH sensor. Inset, experiment schematics.
[0208] FIG. 13. TEM images of ultrathin 60.degree. nanowire probes.
The segment lengths between adjacent 120.degree. cis-kinks in (A)
and (C) are .about.50 nm and .about.15 nm, respectively. (B) and
(D) are high-resolution TEM images recorded in the square regions
of single 120.degree. kinks marked in (A) and (C), respectively.
HRTEM images show that the nanowires are single crystalline and
that their arms follow the <112> growth orientation ((B),
(D), arrows), as previously described in U.S. Provisional Patent
Application Ser. No. 61/245,641, filed Sep. 24, 2009, entitled
"Bent Nanowires," by Tian et al., which is incorporated herein by
reference. All TEM images were acquired with the electron beam
perpendicular to the 2D plane of the kinked nanowires. Scale bars,
50 nm in (A) and (C), and 2 nm in (B) and (D).
[0209] FIGS. 16A and 16B. Kinked nanowire probe characterization in
aqueous solution. (A) Conductance vs. water-gate voltage
measurement for a typical free-standing nanowire probe device. The
device sensitivity is 6.8 microsiemens/V in PBS solution. The data
was recorded with a 100 mV DC source voltage, and the current was
amplified with a home-built multi-channel current/voltage
preamplifier, filtered with a 3 kHz low pass signal conditioner
(CyberAmp 380), and digitized at a 50 kHz sampling rate (Axon
Digi1440A). (B) Calibrated nanowire surface potential change vs.
solution pH. The slope of the linear fit (dashed line) yields a pH
sensor response of .about.59.7 mV/pH. The sensitivity limit is
.about.0.02 pH, with S/N >1.3. The error bars denote .+-.1
standard deviation. Data was recorded in a microfluidic channel as
illustrated in FIG. 10D, inset. The pH sensing measurements were
conducted using a lock-in amplifier with a modulation frequency of
79 Hz, time constant of 30 ms, amplitude of 30 mV. The DC
source-drain potential is zero. A Ag/AgCl reference electrode was
used in (A) and (B).
EXAMPLE 11
[0210] The possibility of establishing an electrical interface
between single cells and solid state semiconductor devices
intracellularly was investigated in this example (FIG. 11A). As
stable and self-healing elements, phospholipid bilayers can fuse
with each other. Thus, the 60.degree. kinked nanowires were
modified with phospholipids
(1,2-dimyristoylsn-glycero-3-phosphocholine (DMPC)) by fusing
unilamellar vesicles onto the negatively charged nanowire surface.
Fluorescence microscopy images show that DMPC lipid bilayers formed
a continuous shell on the silicon nanowire core (FIG. 11B). Without
wishing to be bound by any theory, it is proposed that when a cell
is brought into contact with the hybrid core-shell nanowire (FIG.
11A, I), the lipid bilayers from nanowire shell and cell membrane
fuse together, which exposes the tip of the silicon core to the
cytosol (FIG. 11A, II). Subsequently, the nanoscale FET sensor
(shaded middle segment) enters the cell (FIG. 11A, III) and is
sealed with the fused membrane.
[0211] As a proof-of-concept demonstration of intracellular
electrical recording, the calibrated potential change of one kinked
nanowire probe (FIGS. 11B and 11C) was monitored upon its cellular
entrance into an isolated HL-1 cell (FIG. 11C, I, II, III). A glass
micropipette (inner tip diameter, .about.5 micrometers) was used to
pick up one cell from suspension and hold its intracellular
potential at -50 mV. Then, the same micropipette was used to
approach the cell onto the lipid-coated nanowire tip at a speed of
-30 micrometers/s with an x-y-z micromanipulator. Measurement of
the potential versus time from the FET device showed a sharp
.about.52 mV drop within 250 ms after cell/tip contact, and the
potential maintained at .about.46 mV before going back to the
baseline when the cell was detached from the nanowire by pulling
(.about.30 micrometers/s). Control experiments using a nanowire
probe device without a lipid shell yielded <1.5 mV potential
fluctuation upon cell/tip contact (FIG. 11D), which corroborates
the proposed model (FIG. 11A) and suggests that membrane fusion is
a possible mechanism of assisting device intracellular entrance. In
addition, the marginal conductance/potential change (FIG. 11D) as
the nanowire itself was deformed by the HL-1 cell, which further
confirms that the free-standing nanoscale FET device is
electrically robust (FIG. 10C).
[0212] FIGS. 11A-11D. Surface modification and cellular entrance.
(A) Schematics of nanowire entrance into a cell. This diagram shows
heavily doped nanowire segments (lighter shaded segments on the
bent wire), active sensor segment (darker shaded segments), and the
cytosol (upper quarter circle), and phospholipid bilayers
(surrounding the wire and the cytosol), respectively. (B)
Flurorescence image of a lipids coated nanowire probe. DMPC was
doped with 1% NBD-dye labeled lipids and the hybrids were imaged
through a 510/21 band pass filter. (C) Differential interference
contrast (DIC) microscopy images (upper panel) and electrical
recording (lower panel) of an HL-1 cell interacting with a
60.degree. kinked nanowire probe: I) approaching, II) penetration,
and III) withdrawal. Dashed line, micropipette holding potential.
Scale bars: 5 micrometers. (D) Electrical recording with a
60.degree. kinked nanowire probe without phospholipids surface
modification. Down and up arrows in (C) and (D) mark the beginnings
of cell penetration and withdrawal, respectively.
EXAMPLE 12
[0213] The potential of the devices in interfacing with cultured
electrogenic cells was evaluated in this example. To this end,
interfaces between the freestanding FETs and embryonic chicken
cardiomyocytes were established using a previously described
method, in which the PDMS/cardiomyocyte cell substrates were
positioned using a micromanipulator under an optical microscope to
bring cells into direct contact with devices (FIG. 12A).
[0214] Measurements of the conductance versus time from a
free-standing FET probe in gentle contact with a spontaneously
beating cardiomyocyte cell monolayer (FIG. 12B) showed the
following sequential features (FIG. 12C). Firstly, the regularly
spaced spikes were immediately recorded with a frequency of about
2.3 Hz, a signal-to-noise ratio (S/N).gtoreq.2, a sub-microsecond
duration, and a calibrated negative potential change of .about.3-5
mV (FIG. 12C, I and FIG. 12D, I). The signal amplitude, the shape,
and the sign (FIG. 12D, I) all agreed with the extracellular
recordings. Although the S/N was poorer, it was consistent with the
increased noise in short channel FET devices as used in this study.
The nanowire/cell junction was likely filled with lipid layers from
both the cell membrane and the probe shell (FIG. 12A, II), and the
junction tightness in such protruding configurations can likely be
improved by the nanowire lipid coating. These results highlight the
ability to achieve extracellular recordings using a nanoscale and
free-standing detector and suggest the potential to interface with
biological tissues such as brain slices in 3D.
[0215] Next, after the initial .about.40 s upon the device/cell
contact, several pronounced signal changes were observed (FIG. 12C,
II and III). Firstly, the original extracellular recording signals
gradually disappeared (FIG. 12C, II, lower stars). Secondly, with
concomitant drop in baseline, new peaks with an opposite sign and
much larger amplitude and duration emerged (FIG. 12C, II, upper
stars) and then became steady (FIG. 12C, III). The largest
calibrated amplitude of the stabilized recordings (FIG. 12C, III),
.about.80 mV, and the .about.200 ms signal duration were close to
those in whole-cell patch clamp recordings from cardiomyocytes and
suggest that the electrical interface may have switched from
capacitive extracellular coupling to Ohmic intracellular coupling.
Thirdly, a zoom-in image of one of the later steady recordings
(FIG. 12D, III) showed five characteristic phases of a cardiac
intracellular potential: a) resting state, b) rapid depolarization,
c) plateau, d) rapid repolarization, and e) hyperpolarization. In
addition, the sharp transient peak (upper star) and the notch
(lower star), mostly due to the inward sodium and outward potassium
currents, could also be resolved. These features confirm that
intracellular recordings from cardiomyocytes were achieved using
two-terminal nanoscale FET devices. Finally, the steady
intracellular recording (FIG. 12C, III) from the beating
cardiomyocyte suggests a secure sealing with phospholipids layers
and further corroborates the robustness of the nanowire
devices.
[0216] Notably, close inspection of the transitional recordings
(FIG. 12C, II) revealed additional important features. Firstly, the
switching from extracellular to intracellular signals was smooth
and without appreciable change in recording frequency. This
suggests that the cellular entrance by the nanowire probe tip was
less invasive and did not affect the electrogenic cell firing
patterns. Such a natural transition may be a result of biomimetic
membrane fusion that exposes the silicon nanowire tip directly into
the cytosol (FIG. 11A and FIG. 12A, III). Second, the disappearance
of extracellular signals, after the intracellular ones become
dominant, suggests that the extracellularly exposed contacts and
heavily doped silicon segments did not have a major contribution to
the observed extracellular signals. It also confirms that
two-terminal electrical recording was highly localized to the
nanoscale FET segment near the probe tip. Third, the extracellular
spikes were aligned with the position in intracellular ones where
sodium influx initiated (FIG. 12D, II) and were temporally
separated from the cardiac contraction (FIG. 12D, II, the regime
between dashed lines), suggesting that the recorded extracellular
signals (FIG. 12C, I) were not due to mechanical motion of the
beating cells.
[0217] FIGS. 12A-12D. Electrical recording from cardiomyocytes. (A)
Schematics of cellular recording from cardiomyocyte monolayer on
PDMS (left panel), and zoomed-in extra- and intracellular
nanowire/cell interfaces (right panels). The cell membrane and
nanowire lipids coatings are marked as lines. (B) DIC images of
cells and the device used in extra- and intracellular measurements.
Arrows mark the nanowire tip and electrodes (left panel--nanowire
tip; right panel--two electrodes surrounding a nanowire tip). Scale
bars, 10 micrometers. (C) and (D) Electrical recording from beating
cardiomyocytes. I) extracellular recording. II) a transition from
extracellular to intracellular recordings during cellular entrance,
and III) steady intracellular recording. (D) Zoom-in signals from
the dashed square regions in (C).
EXAMPLE 13
[0218] This example describes various methods used in the above
examples.
[0219] Nanowire synthesis and characterization. Single-crystalline
nanowire probes were synthesized by a pressure modulated
nanocluster-catalysed VLS method to generate kinks. In a typical
synthesis of uniform n-type, 80 nm, 60.degree. bent silicon
nanowires, the flow rates of SiH.sub.4, PH.sub.3 and H.sub.2 were
1-2, 2-10, and 60 standard cubic centimeters per minute,
respectively, and the total pressure 40 torr and purge duration
10-15 s; the time interval between two purges is 20-40 s. In dopant
modulated silicon nanowires, the silicon-phosphorus feed-in ratios
were 200:1 and 10,000:1 for n+- and n-type segments, respectively,
and the n-type segment was grown for 30 s. Zeiss Ultra55/Supra55VP
field emission SEMs and a JEOL 2010 field-emission TEM were used to
carry out SEM and TEM analyses, respectively.
[0220] Device fabrication. Devices were fabricated on silicon
substrates (Nova Electronic Materials, n-type 0.005 V cm) with
100-nm thermal oxide and 200-nm SiN at the surface. Briefly, a
poly(methyl methacrylate) (PMMA) layer was first patterned by
e-beam lithography. Next, SU-8 2000.5 photoresist was spun-coated
onto the substrate, and bent nanowires dispersed in isopropyl
alcohol were deposited onto SU-8 layer. Then, .about.300-400 nm
SU-8 micro-ribbon features were formed by e-beam lithography and
baking (180.degree. C., 20 min). Next, methyl methacrylate (MMA)
and PMMA double layers were spincoated and a last step of e-beam
lithography was used to pattern the contact electrodes and
passivation layers. Finally, Cr (1.5 nm)/Pd(50-80 nm)/Cr(50-80 nm)
and 40-60 nm silicon nitride layers were deposited on SU-8
micro-ribbons by thermal evaporation and plasma enhanced chemical
vapor deposition. The complete bent devices are self-actuated after
lift-off process in acetone. See also FIG. 14.
[0221] Cellular recordings. HL-1 cells and embryonic chicken
cardiomyocytes were cultured using the published protocols. The
device chips were cleaned with O.sub.2 plasma and the nanowire
surfaces were then modified by vesicle fusion with a blend solution
of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and an
NBD-labelled lipid,
1-myristoyl-2-{12-[(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]dodecan-
oyl}-sn-glycero-3-phosphocholine. Nanowire recording was carried
out in Tyrode solution with a 100 mV DC source voltage. The current
was amplified with a home-built multi-channel current/voltage
preamplifier, and a 3000 Hz low pass signal conditioner (CyberAmp
380), and digitized at a 50 kHz sampling rate (Axon Digi1440A).
Voltage clamp was performed with an Axopatch 200B from Molecular
Device Systems using glass pipettes pulled on a P-97
Flaming/BrownMicropipette Puller (Sutter Instruments). Ag/AgCl
reference electrode was used in all recordings.
[0222] FIGS. 14A and 14B. 60.degree. bent nanowires with integrated
transistor elements. (A) (left) Optical micrograph of five
60.degree. kinked nanowire structures; scale bar is 20 micrometers.
The white numbers correspond to Au-metal markers defined on the
device chip prior to deposition of the kinked nanowires. The middle
and the right panels are the zoom-in optical microscopy images of
nanowire 2 and 4, respectively. The images were recorded in
bright-field mode. (B) Atomic force microscopy (AFM, left) and
scanning gate microscopy (SGM, middle & right) images of a
60.degree. kinked nanowire device. The scale bar in the AFM image
is 2 micrometers. Measurements were carried out with a Digital
Instruments Nanoscope Ma MultiMode AFM and metal-coated tips
(Nanosensors, PPP-NCHPt). The SGM conductance maps were acquired in
lift mode with lift height of 20 nm. The SGM images were recorded
with a V.sub.tip of +10 V (middle) and -10 V (right), respectively,
and V.sub.sd of 0.5 V. The device conductance is 4.2 microsiemens.
The dark and bright regions correspond to reduced and enhanced
conductance, respectively. The SGM data demonstrate the successful
synthetic integration of an n-type field effect transistor (FET)
immediately adjacent to the 60.degree. probe tip, where the length
of the active region of the FET is .about.200 nm.
[0223] FIG. 15. Free-standing kinked nanowire probe fabrication.
(A) Key fabrication steps include: (1) deposition and patterning of
poly(methylmethacrylate) (PMMA) layer by electron-beam lithography
(EBL); (2) deposition of SU-8 2000.5 photoresist over the entire
chip; (3) deposition of kinked nanowires from isopropanol solution;
(4) EBL patterning and subsequent curing (180.degree. C., 20 min)
of 300-400 nm SU-8 structure that will serve as flexible mechanical
support for metal contacts; (5) deposition and (6) EBL patterning
of methyl methacrylate (MMA) and PMMA double layers resist; and
finally, (7) sequential Cr/Pd/Cr (1.5/50-80/50-80 nm) contact
thermal evaporation and plasma-enhanced chemical vapor deposition
of 40-60 nm Si.sub.3N.sub.4 contact passivation. The kinked
nanowire probe devices are released from the (substrate) by removal
of the initial PMMA layer during the lift-off process in acetone,
where the built in stress in the Pd/Cr electrodes leads to
predictable height and angle of the nanowire probe with respect to
the substrate surface. The device tip is detailed in panel-8. (B)
Dependence of the tip height and angle versus the length of
relieved metal. The measurements were done in PBS solution for
metal layers with Cr/Pd/Cr thickness of 1.5/75/50 nm. Inset,
schematic of the device geometry; the typical nanowire arm length
is 10 micrometers.
[0224] While several embodiments of the present invention have been
described and illustrated herein, those of ordinary skill in the
art will readily envision a variety of other means and/or
structures for performing the functions and/or obtaining the
results and/or one or more of the advantages described herein, and
each of such variations and/or modifications is deemed to be within
the scope of the present invention. More generally, those skilled
in the art will readily appreciate that all parameters, dimensions,
materials, and configurations described herein are meant to be
exemplary and that the actual parameters, dimensions, materials,
and/or configurations will depend upon the specific application or
applications for which the teachings of the present invention
is/are used. Those skilled in the art will recognize, or be able to
ascertain using no more than routine experimentation, many
equivalents to the specific embodiments of the invention described
herein. It is, therefore, to be understood that the foregoing
embodiments are presented by way of example only and that, within
the scope of the appended claims and equivalents thereto, the
invention may be practiced otherwise than as specifically described
and claimed. The present invention is directed to each individual
feature, system, article, material, kit, and/or method described
herein. In addition, any combination of two or more such features,
systems, articles, materials, kits, and/or methods, if such
features, systems, articles, materials, kits, and/or methods are
not mutually inconsistent, is included within the scope of the
present invention.
[0225] All definitions, as defined and used herein, should be
understood to control over dictionary definitions, definitions in
documents incorporated by reference, and/or ordinary meanings of
the defined terms.
[0226] The indefinite articles "a" and "an," as used herein in the
specification and in the claims, unless clearly indicated to the
contrary, should be understood to mean "at least one."
[0227] The phrase "and/or," as used herein in the specification and
in the claims, should be understood to mean "either or both" of the
elements so conjoined, i.e., elements that are conjunctively
present in some cases and disjunctively present in other cases.
Multiple elements listed with "and/or" should be construed in the
same fashion, i.e., "one or more" of the elements so conjoined.
Other elements may optionally be present other than the elements
specifically identified by the "and/or" clause, whether related or
unrelated to those elements specifically identified. Thus, as a
non-limiting example, a reference to "A and/or B", when used in
conjunction with open-ended language such as "comprising" can
refer, in one embodiment, to A only (optionally including elements
other than B); in another embodiment, to B only (optionally
including elements other than A); in yet another embodiment, to
both A and B (optionally including other elements); etc.
[0228] As used herein in the specification and in the claims, "or"
should be understood to have the same meaning as "and/or" as
defined above. For example, when separating items in a list, "or"
or "and/or" shall be interpreted as being inclusive, i.e., the
inclusion of at least one, but also including more than one, of a
number or list of elements, and, optionally, additional unlisted
items. Only terms clearly indicated to the contrary, such as "only
one of" or "exactly one of," or, when used in the claims,
"consisting of," will refer to the inclusion of exactly one element
of a number or list of elements. In general, the term "or" as used
herein shall only be interpreted as indicating exclusive
alternatives (i.e. "one or the other but not both") when preceded
by terms of exclusivity, such as "either," "one of," "only one of,"
or "exactly one of." "Consisting essentially of," when used in the
claims, shall have its ordinary meaning as used in the field of
patent law.
[0229] As used herein in the specification and in the claims, the
phrase "at least one," in reference to a list of one or more
elements, should be understood to mean at least one element
selected from any one or more of the elements in the list of
elements, but not necessarily including at least one of each and
every element specifically listed within the list of elements and
not excluding any combinations of elements in the list of elements.
This definition also allows that elements may optionally be present
other than the elements specifically identified within the list of
elements to which the phrase "at least one" refers, whether related
or unrelated to those elements specifically identified. Thus, as a
non-limiting example, "at least one of A and B" (or, equivalently,
"at least one of A or B," or, equivalently "at least one of A
and/or B") can refer, in one embodiment, to at least one,
optionally including more than one, A, with no B present (and
optionally including elements other than B); in another embodiment,
to at least one, optionally including more than one, B, with no A
present (and optionally including elements other than A); in yet
another embodiment, to at least one, optionally including more than
one, A, and at least one, optionally including more than one, B
(and optionally including other elements); etc.
[0230] It should also be understood that, unless clearly indicated
to the contrary, in any methods claimed herein that include more
than one step or act, the order of the steps or acts of the method
is not necessarily limited to the order in which the steps or acts
of the method are recited.
[0231] In the claims, as well as in the specification above, all
transitional phrases such as "comprising," "including," "carrying,"
"having," "containing," "involving," "holding," "composed of," and
the like are to be understood to be open-ended, i.e., to mean
including but not limited to. Only the transitional phrases
"consisting of" and "consisting essentially of" shall be closed or
semi-closed transitional phrases, respectively, as set forth in the
United States Patent Office Manual of Patent Examining Procedures,
Section 2111.03.
* * * * *